Дисертації з теми "Lymphocyte activity"
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1
Chu, Nelson Randall. "Characterization of a T lymphocyte-derived, antigen-binding molecule with suppressive activity." Thesis, University of British Columbia, 1989. http://hdl.handle.net/2429/30608.
Повний текст джерелаАнотація:
Regulation of the immune response is mediated, in part, by the action of suppressor T cells (Ts). One intriguing aspect of these cells is the description of T cell suppressor factor (TsF): a soluble analog of the cell that shares many of its properties, such as the ability to bind free antigen (Ag) and suppress an Ag-specific immune response. The exact molecular nature of TsF and the relationship of TsF to Ts are unknown. The immune response to the small, bacterial protein, ferredoxin (Fd), was used as a model system to study TsF. A Fd-specific suppressor cell network has been described in mice that are genetically nonresponsive to this Ag. Previously, a soluble mediator, known as Fd11F, was found in the culture supernatant (SN) of the Ts hybridoma, Fd11. Fd11F possessed both Ag-binding activity and the ability to suppress the anti-Fd Ab response in mice. The TsF-specific monoclonal antibody, B16G, was used for both the recovery of Fd11F-enriched material from SN and its detection by the enzyme-linked immunosorbent assay. ' Further immunochemical, biological, and biochemical characterization of Fd11F was done with emphasis on describing the Ag-binding properties of Fd11F. It was found that Fd11F bound to solid- and liquid-phase Fd, and demonstrated preferential binding to the carrier determinant of the Ag. A spleen cell culture assay was devised which showed that Fd11F suppressed Ab production in a concentration-dependent manner. Additional experiments suggested that the suppressive effect was
Ag-specific. The identification of the Ag-binding molecule was attempted by the fractionation of Fd11F-enriched material using high performance gel filtration or preparative SDS-PAGE (run under non-reducing conditions). Using SDS-PAGE, a unique, single polypeptide of about 30k relative molecular mass (Mr) was identified as the Ag-binding moiety of Fd11F. The possible relationship of this moiety to other identified materials is discussed.Science, Faculty of
Microbiology and Immunology, Department of
Graduate
2
Endicott, Roger A. "Immunoregulation of T-lymphocyte proliferative activity by alveolar macrophages from mice bearing Lewis lung carcinoma tumors." Virtual Press, 1986. http://liblink.bsu.edu/uhtbin/catkey/458971.
Повний текст джерелаАнотація:
The immune regulatory abilities of alveolar macrophages from C57B1/6 mice bearing a metastatic variant of Lewis lung carcinoma were determined. During early stages of tumor development, or before tumors metastasized to the lungs, alveolar macrophages did not affect or slightly enhanced T-lymphocyte proliferation; as tumor growth progressed, or following tumor metastasis, alveolar macrophages suppressed the T-cell response. Macrophage suppressor activity was probably not mediated by their production of PGE, since macrophages of tumor-bearing mice secreted less 2 PGE than did macrophages of normal mice. Normal alveolar 2 macrophages or macrophages preincubated in tumor cell supernatant for a short period stimulated T-cell blastogenesis and secreted PGE during in vitro culture. However, with 2 longer exposure to tumor cell supernatant, alveolar macrophages lost the capacity to augment T-cell proliferation and secreted less PGE 2.Ball State UniversityMuncie, IN 47306
3
Glashoff, Richard Helmuth. "Characterisation of cytolytic CD4+ and suppresor CD8+ activity of T lymphocyte clones derived from tuberculous pleuritis." Doctoral thesis, University of Cape Town, 2000. http://hdl.handle.net/11427/3390.
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4
Kane, Kim Kartchener. "In Vitro Identification of the Effect of Serotonin on Lymphocyte DNA Synthesis and Natural Killer Cell Activity." DigitalCommons@USU, 1989. https://digitalcommons.usu.edu/etd/5863.
Повний текст джерелаАнотація:
The purpose of this study was to identify the effects of the neurotransmitter, serotonin (SE), on the immune function of peripheral blood mononuclear cells (PBMC) of normal, healthy subjects. This was done as a preliminary investigation to studies on the association of SE with immune changes in autistic subjects.
The PBMC isolated from normal male subjects were treated with various concentrations of SE for 48 hrs. Their incubation in SE at a concentration of 10-3 M induced about a 35% decrease in DNA synthesis. However, incubation of the cells in lower concentrations (10-4 to 10-10) of SE produced no significant effect. The ability of natural killer (NK) cells to lyse K562 target cells was also examined after incubation with SE for 48 hrs. The NK activity was almost completely eliminated following incubation in 10-3M of SE, but the activity was not significantly decreased by exposure to lower concentrations of SE. The viability of PBMC was not altered following incubation with SE under identical conditions as those utilized in the NK assay.
Preliminary analysis using a fluorescence-activated cell sorter (FACS) of monoclonal antibodies directed against Tll (total T cell), T4 (helper T cell), T8 (suppressor and cytotoxic T cells), B-cell and NK cell markers indicated that the suppressive effect exerted by SE could be attributed to a decrease in the density of these markers or receptors on the cell surface. These findings provide additional evidence for a possible link between neurotransmitters, specifically SE, and immune function.
5
Zheng, Chengyun. "Genetic polymorphisms and natural killer cell activity in multiple myeloma /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-222-1.
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6
Adewusi, Iyabode Olukemi 1958. "The Eosinophil and Lysophospholipase Responses in Mice Infected with Trichinella spiralis: A Role for the Lymphocyte and Macrophage." Thesis, North Texas State University, 1986. https://digital.library.unt.edu/ark:/67531/metadc331042/.
Повний текст джерелаАнотація:
The relationship among eosinophils, lysophospholipase activity and the immune response in animals infected with Trichinella spiralis was studied using in vivo and in vitro techniques. In an in vivo experiment, anti-thymocyte serum (ATS) was administered to mice infected with T. spiralis and its effects on intestinal lysophospholipase (EC 3.1.1.5.) activity, peripheral blood, bone marrow and intestinal eosinophilia were measured in the same experimental animal. The ATS caused a significant temporally related suppression of both the tissue lysophospholipase response and eosinophilia, in all three compartments. These findings support the hypothesis that parasite-induced eosinophilia is the cause of the increased lysophospholipase activity of parasitized tissue and that the responses are thymus cell-dependent. In vitro experiments demonstrated that the eosinophil was the primary inflammatory cell source of lysophospholipase among eosinophils, neutrophils macrophages and lymphocytes. The role of other cells and antigen in the production of the enzyme by the eosinophil was also investigated in vitro• Results demonstrated that eosinophils cultured with both T. spiralis antigen and other leukocytes yielded enzyme activities significantly greater than eosinophils cultured alone or with only antigen. More specific experiments showed that T-lymphocytes were the cells responsible for influencing the eosinophils' lysophospholipase activity in the presence of antigen, and that their influence was enhanced by the presence of macrophages. These results suggested that increased lysophospholipase activity present in parasitized tissue was not only due to increased numbers of eosinophils infiltrating parasitized tissue but was also due to each eosinophil synthesizing more of the enzyme. The necessity for antigen and other cells suggests a role for cell cooperation in the production of the enzyme, specifically T-lymphocytes and macrophage interaction with the eosinophil. A lymphocyte soluble factor collected from sensitized lymphocytes stimulated with specific antigen or concanavalin A was found to enhance the eosinophil lysophospholipase activity when added to cultures of eosinophils plus other peritoneal cells. The soluble factor did not stimulate the lysophospholipase activity of pure cultures of eosinophils.
7
Marcellon, Roselande. "Profiling patients with type 2 diabetes on the paradox idea: the underappreciated role of toll-like receptors in B lymphocyte activity." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12504.
Повний текст джерелаАнотація:
Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Type 2 diabetes (T2D) is a growing concern in most developed countries and in the US. The disease is associated with increased risk for certain diseases such as cardiovascular disease, kidney disease, retinopathy, neuropathies, dementia and most types of cancers. Many studies have established an association between chronic inflammation and diabetes pathology. Part of the pathology of T2D involves a chronic state of inflammation in which the immune response is altered. Toll-like receptors (TLRs), specifically Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4), play critical roles in mediating inflammation. Past studies have looked at the role TLRs play, but have not characterized their combined effects or the influences of other covariates such as various clinical and immunological parameters. This study aimed to investigate the role of TLRs, specifically TLR2 and TLR4, in B lymphocytes and how this expression can be used to profile and characterize disease severity in patients with T2D. This study used a subset of patients (n=SO) enrolled in an IRB approved and industry sponsored study in the Ganley-Leal lab in the Section of Infectious Disease Laboratory at Boston University Department of Medicine. Patient data was obtained from medical records, a short questionnaire, and heparinized blood samples. Serum concentrations of High Mobility Group Protein 1 (Hmgbl) and Limulus Amebocyte Lysate (endotoxin) were measured along with B lymphocyte TLR expression and cellular responses to TLR ligands. Bivariate tests, tests for linear associations and an analysis of variance (ANOVA) were performed on clinical, immunologic and disease severity index parameters. The study found that TLR2 expression on B cells was both significantly associated and correlated positively with triglyceride levels. High basal IL-8 production was important in characterizing level of response for clinical parameters. The data suggests that IL-8 production and DSI score, in conjunction with TLR2 expression by B cells, can help profile patients with T2D and characterize additional risks that may be overlooked when using parameters like glycated hemoglobin. Further research is needed to explore the role of B cells and TLR activity in chronic inflammatory processes and in patients with chronic inflammatory diseases such as T2D.
8
Lecron, Jean-Claude. "Caractérisation biologique et physico-chimique d'un facteur "prothymocyte differentiating activity" (ptda) capable de promouvoir la différenciation et l'activation de lymphocytes T humains." Poitiers, 1988. http://www.theses.fr/1988POIT2270.
Повний текст джерелаАнотація:
La differenciation lymphocytaire t obeit a des mecanismes complexes faisant extervenir des interactions cellulaires de contact et des facteurs solubles. Les techniques de clonage lymphocytaire t en milieu semi solide ont permis de mettre en evidence un facteur doue d'une activite differenciatrice vis a vis de prothymoxytes medullaires humains (ptda). Ce facteur est produit, par les cellules b + nulles du sang peripherique stimulees par la phytohemagglutinine. Des etudes sequentielles suggerent que la ptda agit non comme un facteur de proliferation mais comme un signal de differenciation des prothymocytes et de preactivation des lymphocytes t cd4+
9
Gannon, Gregory Allan. "Peripheral blood lymphocyte trafficking and natural killer cell cytolytic activity during prolonged, exhaustive aerobic exercise, a focus on cell adhesion molecules and ß-endorphin." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0002/NQ35159.pdf.
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10
Santoro, Lyse. "Appretement et présentation d'un anticorps monoclonal murin par une lignée monocytaire ou lymphocytaire B humaine : influence de la liaison covalente entre anticorps et fragment C3b du complément." Grenoble 1, 1994. http://www.theses.fr/1994GRE10126.
Повний текст джерелаАнотація:
La proteine c3 du complement influence l'elaboration de la reponse immune specifique dirigee contre un antigene defini. L'etude presentee dans cette these contribue a demontrer que le fragment c3b du complement, en se fixant de facon covalente a un antigene d'origine exogene, module l'appretement de l'antigene par une cellule presentatrice de l'antigene. Des donnees bibliographiques recentes concernant l'appretement d'antigenes, le fragment c3b et son implication dans la reponse immune specifique sont presentees dans un chapitre d'introduction. L'etude experimentale decrite a ete realisee en utilisant des anticorps monoclonaux murins comme antigenes et des cellules monocytaires ou lymphocytaires b humaines comme cellules presentatrices ; des complexes covalents anticorps monoclonaux-c3b ont ete produits et caracterises. Les resultats obtenus sont exposes dans trois chapitres. Dans un premier chapitre, des experiences montrent que la presentation d'anticorps monoclonaux murins a des cellules t humaines specifiques de ces anticorps est modulee lorsqu'ils sont complexes au fragment c3b. Puis certaines des principales etapes de l'appretement des anticorps utilises sont caracterisees dans des cellules monocytaires u937 ou lymphocytaires b humaines non specifiques de l'antigene (fixation a des recepteurs membranaires, internalisation, transit intracellulaire, modifications biochimiques) ; enfin, l'influence de la liaison covalente entre anticorps et c3b sur ces differentes etapes est mise en evidence. Des hypotheses sont proposees concernant un role chaperon de c3b
11
Mitchell, Jeffrey Tullis. "Immunological Effects of Ketoconazole, Itraconazole and Fluconazole on Lymphocyte Cell Proliferation and Natural Killer Cell Activity in Immune-Normal, Cyclosporine-Compromised and Cyclophosphamide-Compromised Mouse Models." DigitalCommons@USU, 1990. https://digitalcommons.usu.edu/etd/4666.
Повний текст джерелаАнотація:
Over the past several years there has been a steady increase in the incidence of immunologically compromised patients. This has been the result of both chemical agents, such as those used in cancer chemotherapy, and biological agents such as HIV, the cause of Acquired lmmunodefeciency Syndrome (AIDS). The increase in immune-suppressed patients has lead to an increase in life-threatening mycoses requiring treatment with antifungal agents. Pharmaceutical companies have increased research for the development of new antifungal agents which are more effective and less toxic than those that are currently used. Several researchers have reported on antifungal agents that demonstrate both positive and negative effects on the immune system. Because antifungal therapy relies on host immune defenses in eliminating diseases, more emphasis is being placed on how antifungal agents interact with the immune system. The purpose of this study was to evaluate the effects of Ketoconazole, ltraconazole and Fluconazole on T- and B-cell proliferation and natural killer cell activity using normal, cyclosporine-compromised and cyclophosphamide-compromised immune models in mice. T and B cells obtained from the spleens Balb/c mice were mitogen stimulated and grown in the presence of 0, 1, 2, 4, 8 and 16 µg/ml of these 3 antifungal agents. Cell proliferation was determined by the uptake of 3[H]-thymidine and was measured as counts per minute. Natural killer cell activity was measured by the release of 51-sodium chromate (51Cr) into the supernatant by 51Cr-labeled Yac cells. Ketoconazole caused a significant reduction in cell proliferation in all immune models in both T and B cells. Itraconazole also significantly inhibited cell proliferation in all models in both T and B cells as well as natural killer (NK) cell activity in the immune-normal model. Viability studies on mitogen-stimulated lymphocytes suggest that inhibitory effects of Katoconazole and Itraconazole on lymphocyte proliferation are due to toxic effects. Fluconazole appears to have few if any inhibitory effects on either cell proliferation or natural killer cell activity.
12
Cholley-Cohen, Tanugi Laurence. "La NADPH oxydase des lymphocytes B immortalisés par le virus d'Epstein-Barr : étude d'un cas de granulomatose chronique lié à un déficit en facteur cytosolique d'activation p67phox." Université Joseph Fourier (Grenoble), 1994. http://www.theses.fr/1994GRE10153.
Повний текст джерелаАнотація:
Ce travail a pour objectif l'analyse de la nadph oxydase des lymphocytes b immortalises par le virus d'epstein-barr (lb-ebv). Dans la premiere partie du memoire, le systeme de production des ions superoxyde des lymphocytes b immortalises est compare a celui des polynucleaires neutrophiles. La mise au point d'un test d'activation de l'enzyme en milieu acellulaire et en systeme heterologue, complete par l'utilisation de techniques immunochimiques montre des proprietes similaires du complexe oxydase dans les deux modeles cellulaires bien que l'activite enzymatique engendree dans les lymphocytes b-ebv stimules soit faible. Dans une deuxieme partie un cas particulier de granulomatose chronique presentant un deficit en facteur cytosolique de 67 kda est analyse au niveau moleculaire. L'anomalie genetique a l'origine de la maladie est mise en evidence sur l'arn messager et l'adn genomique de la patiente grace aux techniques de biologie moleculaire (amplification par polymerisation de chaine, clonage et sequencage) en utilisant les lymphocytes b immortalises comme materiel de travail. Les resultats experimentaux revelent une mutation ponctuelle au niveau du site d'epissage (extremite 5') de l'intron 3 ; cette mutation est a l'origine de l'absence de rna messager codant le facteur p67#p#h#o#x
13
Kahi, Sandrine. "Activité lymphocytaire spécifique au cours de la toxoplasmose congénitale humaine." Lyon 1, 1999. http://www.theses.fr/1999LYO1T126.
Повний текст джерела
14
Morrison, Alan R. "Poly(ADP)-Ribose Polymerase Activity in the Eukaryotic Mono-ADP-Ribosyl Transferase, ART2: a Dissertation." eScholarship@UMMS, 2003. https://escholarship.umassmed.edu/gsbs_diss/126.
Повний текст джерелаАнотація:
The glycophosphatidylinositol(GPI)-linked membrane protein ART2 is an antigenic determinant for T lymphocytes that regulate the expression of diabetes in the BB/W rat model. Though little is understood of the physiologic role of ART2 on T lymphocytes, ART2 is a member of the mono-ADP-ribosyl transferase subgroup ofthe ADP-ribosyl transferase (ART) protein family. The ART protein family, which traditionally has been divided into mono-ADP-ribosyl transferases (mono-ARTs), poly(ADP)-ribose polymerases (PARPs), and ADP-ribosyl cyclases, influences various aspects of cellular physiology including: apoptosis, DNA damage repair, chromatin remodeling, telomere replication, cellular transport, immune regulation, neuronal function, and bacterial virulence. A structural alignment of ART2.2 with chicken PARP indicated the potential for ART2.2 to catalyze ADP-ribose polymers in an activity thought to be specific to the PARP subgroup and important for their regulation of nuclear processes. Kinetic studies determined that the auto-ADP-ribosyl transferase activity of ART2.2 is multitmeric and heterogeneous in nature. Hydroxylamine-cleaved ADP-ribose moieties from the ART2.2 multimers ran as polymers on a modified sequencing gel, and digestion of the polymers with snake-venom phosphodiesterase produced AMP and the poly(ADP)ribose-specific product, PR-AMP, which was resolved by analytical HPLC and structurally confirmed by ESI-MS. The ratio of AMP to PR-AMP was higher than that of PARP raising the possibility that the ART2.2 polymers had a different branching structure than those of PARP. This alternative branching was confirmed by the presence of ribose phosphate polymers in the snake venom phophodiesterase treated samples. The site of the auto-poly(ADP)-ribose modification was determined to be R185, a residue previously proposed to influence the level of auto-ADP ribosylation of ART2.2 by mutational analysis. These data provide the first demonstration of a hybrid between mono-ARTs and PARPs and are the earliest indication that PARP-like enzymes can exist outside the nucleus and on the cell surface.
15
Telvi, Louise. "Effets des immunomodulateurs sur certaines fonctions lymphocytaires T." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37610262p.
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16
Hietter, Hélène. "Activites biologiques des hydroxysterols : cytotoxicite selective et immunomodulation." Université Louis Pasteur (Strasbourg) (1971-2008), 1986. http://www.theses.fr/1986STR13323.
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17
Iferroudjene, Djedjiga. "Complément et réponse immune : effet comitogénique du composant C3 et du facteur H sur les lymphocytes T." Rouen, 1988. http://www.theses.fr/1988ROUES011.
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18
Shidani, Babak. "Effet de la cyclosporine a sur le systeme immunitaire de la souris." Paris 7, 1987. http://www.theses.fr/1987PA077159.
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19
Gaudin, Philippe. "Protéolyse matricielle : étude de la gélatinase-b de 92 KDA et de son inhibiteur specifique le TIMP-1 : application à la polyarthrite rhumatoïde." Université Joseph Fourier (Grenoble), 1998. http://www.theses.fr/1998GRE10052.
Повний текст джерелаАнотація:
La synovite rhumatoïde représente un modèle de processus inflammatoire chronique ou le remodelage pathologique de la matrice extracellulaire est responsable de lésions anatomiques. Il dépend principalement des métalloprotéases matricielles, de certaines protéases à sérine comme les activateurs du plasminogène ou l'élastase des polynucléaires neutrophiles. Ces protéases concourent à une protéolyse focalisée qui dépend de la compartimentation des enzymes protéolytiques, de l'action d'inhibiteurs, spécifiques ou non, de la liaison enzyme-substrat, de l'éventuelle localisation membranaire des enzymes. Les polynucléaires neutrophiles sont présents en grand nombre dans le liquide synovial rhumatoïde. Les lymphocytes T et B, localisés dans la membrane synoviale, participent à la réaction inflammatoire et immune. Nous avons montre que l'élastase des polynucléaires neutrophiles préalablement actives par le PMA se localise en partie a la membrane plasmique et est capable d'activer la gélatinase-B de 92 KDA (MMP-9) dans l'environnement péricellulaire immédiat. D'autre part, nous nous sommes intéressés à la caractérisation des lymphocytes B en métalloprotéases et en inhibiteurs spécifiques tissulaires (TIMP). Nous avons isolé, purifié le TIMP-1 à partir de milieux de culture de lymphocytes B immortalisés par le virus d'Epstein-Barr par quatre étapes de chromatographie. Il a été identifié par spectrométrie de masse, caracterisé sur le plan de son pouvoir inhibiteur sur la gélatinase-B de 92 KDA préalablement activée par l'APMA. Les mécanismes de régulation de son expression ainsi que de celle de la MMP-9 ont été abordés par l'étude de l'influence de certaines cytokines, facteurs de croissance et ligands comme le PMA, le LPS et la concanavaline A, du calcium libre intracellulaire. La sécrétion de TIMP-1 par rapport à celle de MMP-9 dans les milieux de culture est 1000 fois plus importante sans que l'explication en soit claire. Elle est induite par l'IL-10, le TGFf, le LPS, le PMA. Les résultats suggèrent que l'expression de TIMP-1 et celle de la MMP-9, sont étroitement contrôlées. La chélation du calcium libre intracellulaire entraîne une baisse de la synthèse mais également de l'excrétion du TIMP-1. Nous avons dans une dernière partie étudié les taux synoviaux des gélatinases A ou MMP-2 et B ou MMP-9, du TIMP-1 et de la stromélysine-1 (MMP-3) dans 50 prélèvements. L'activité MMP-9, les taux de MMP-3 et de TIMP-1 permettent de caractériser et d'opposer les liquides mécaniques et inflammatoires.
20
Safya, Hanaa. "Modulation des activités du récepteur purinergique P2X7 au cours de l’activation des lymphocytes T." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA11T083/document.
Повний текст джерелаАнотація:
L’ATP extracellulaire, à travers l’activation du récepteur P2X7, joue un rôle important dans l’immunité inné comme signal de danger responsable de l’assemblage de l’inflammasome, de la migration des cellules immunitaires et de la mort cellulaire. Bien que le rôle de la voie ATP/P2X7 dans l’immunité adaptative reste sous-estimé, il a été rapporté que le récepteur P2X7 participe aux mécanismes de signalisation impliqués dans l’activation des lymphocytes T, leur prolifération et leur différentiation. Notre laboratoire a récemment montré que les lymphocytes T effecteurs (CD4+ ou CD8+) en fin de réponse immunitaire secondaire, exprimant à la membrane la tyrosine phosphatase de membrane B220, sont totalement résistant à l’activation du récepteur P2X7 à cause d’une perte d’adressage de ce récepteur à la membrane. Le but de ce travail de thèse est d’étudier la sensibilité des lymphocytes T, à différents stades d’activation, aux activités cellulaires induites par l’ATP, notamment le clivage de la molécule de homing CD62L ou L-sélectine, l’ouverture du canal ionique, la formation du pore et l’externalisation de la PS. Mes principaux résultats montrent que les activités cellulaires dépendantes du récepteur P2X7 sont dissociées. Les lymphocytes T au stade effecteur/mémoire sont moins sensibles au clivage de la molécule CD62L que les lymphocytes T au stade naïf et récemment activé. Les lymphocytes naïfs T récemment activé en réponse immunitaire primaire sont les plus sensibles à la formation du pore. De plus, les lymphocytes T récemment activés, aussi bien en réponse immunitaire primaire que secondaire, sont les plus sensibles à l’externalisation de la PS. Enfin, dans les lymphocytes T récemment activé, les activités de pore et d’externalisation de PS, mais pas le clivage de CD62L, sont dépendantes du taux de calciumExtracellular ATP through the receptor P2X7 (P2X7R) plays a key role in innate immunity as a danger signal that causes the activation of the inflammasome, enhancement of immune cell migration and cell death. Although the role of the ATP/P2X7R pathway in adaptative immunity remains underestimated, it has been reported that P2X7R regulates signaling events involved in T-cell activation, proliferation, and differentiation into effector lineages. Moreover, we have previously shown that effector T lymphocytes (either CD4+ or CD8+) that express the B220 isoform of CD45 at the plasma membrane at the end of the secondary immune response are totally resistant to ATP stimulation due to loss of P2X7R membrane expression. In the present study, we compared the sensitivity of T lymphocytes to cellular activities trigerred by P2X7R according to their stage of activation. Interestingly, our results showed that P2X7-dependent cellular activities are dissociated. T lymphocytes at effector/memory stage are less sensitive to CD62L shedding than naïve or recently activated T lymphocyte during primary immune response. Naive T lymphocytes recently activated during primary immune response are the most sensitive to pore formation. Furthermore, recently activated T lymphocytes at both primary and secondary immune responses are the most sensitive to PS externalization. Finally, pore formation, PS externalization but not CD62L shedding, are dependent on calcium signaling
21
Porter, Joanna Catherine Mary. "Control of leukocyte integrin activity on T lymphocytes." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312850.
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22
Biella, Carla de Agostino. "Avaliação da atividade imunomoduladora de \'Alternanthera tenella\' Colla e investigação de ações do extrato aquoso em modelo de artrite experimental." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-24092010-143641/.
Повний текст джерелаАнотація:
Plantas do gênero Alternanthera (Amaranthaceae) vêm sendo estudadas por suas propriedades antiparasitária, antibacteriana e antiviral. No Brasil a planta Alternanthera tenella Colla, objeto de nossa investigação, é utilizada na medicina popular por possuir atividade antiinflamatória. Considerando a importância do sistema imunológico em infecções e em doenças auto-imunes sistêmicas que apresentam intensa reação inflamatória, o objetivo do atual estudo foi investigar a ação imunomoduladora de extratos de A. tenella no sistema imune de camundongos BALB/c e sua atividade em modelo de artrite experimental induzida pelo óleo mineral pristane (2,6,10,14-tetrametilpentadecano) em camundongos AIRmax, obtidos por seleção genética para reação inflamatória aguda máxima. Extratos brutos orgânicos (etanólico e hexânico), aquosos, frações e flavonóides foram inoculados via intraperitoneal em camundongos BALB/c imunizados ou não com eritrócitos de carneiro (EC). Efeitos imunomoduladores e imunotóxicos foram avaliados através da determinação do peso corporal e dos órgãos linfóides, celularidade do baço e de ensaios funcionais como enumeração de células formadoras de placas (PFC, plaque forming cells), produção de anticorpos anti-EC e edema de pata induzido por carragenina. Posteriormente foram avaliados os efeitos dos extratos aquosos nas subpopulações de linfócitos esplênicos (CD3, CD4, CD8 e CD19), na expressão de marcadores de ativação de linfócitos (CD25, CD40, CD45RB e CD69) e na indução de apoptose nessas células. Os extratos avaliados não induziram alterações no peso dos animais e dos órgãos (baço, timo e fígado) após 4 e 14 dias. Animais imunizados com EC e tratados com o flavonóide 2-O--L-ramnopiranosilvitexina (15 mg/kg), isolado de extrato bruto etanólico (E) ou com o extrato aquoso extraído a frio (AF - 100 mg/kg) apresentaram aumento significativo (p<0,05) no número de PFC anti-EC em comparação aos controles. Os extratos E e AF induziram aumento no título de anticorpos circulantes anti-EC das classes IgG e IgM. Estes resultados sugerem atividade imunoestimulante. Ambos os extratos aquosos, AF e extraído a quente (AQ), apresentaram atividade antiinflamatória no edema de pata induzido por carragenina, principalmente AF que demonstrou efeito dose-dependente (50% e 61% de inibição do edema nas doses de 200 mg/kg e 400 mg/kg, respectivamente). Estes extratos em camundongos BALB/c normais não induziram apoptose, alterações nas subpopulações de linfócitos e não modificaram a expressão de marcadores de ativação em linfócitos T e B. Com base nestes resultados, o extrato AF foi selecionado para utilização nos experimentos em camundongos AIRmax, para investigação de suas possíveis atividades moduladora e/ou terapêutica na artrite induzida por pristane. Os animais que foram tratados com seis doses de 200 mg/kg do extrato AF antes das injeções do pristane (G1, n=15) apresentaram menor incidência de artrite em comparação ao grupo controle positivo, composto por animais que receberam apenas pristane (G4, n=15) (54,5% e 70%, respectivamente). A porcentagem de animais que apresentaram deformidade nas articulações, também foi menor no grupo G1 (18,2%) em comparação ao G4 (30%). Os animais que receberam apenas o extrato (G3, n=14) não apresentaram artrite. Adicionalmente, AF conferiu atividade protetora ao desenvolvimento de ascite, processo inflamatório que também pode ser induzido pelo óleo mineral. As taxas de incidência de ascite nos animais tratados previamente (G1) bem como nos animais tratados após (G2, n=16) as injeções de pristane foram menores do que a do grupo controle positivo (G1=18,2%, G2=6,7% e G4= 50%). Ressalta-se que os índices de sobrevivência nos grupos de animais que receberam o extrato foram superiores ao grupo controle positivo (G1= 86,7%; G2= 93,7%; G4= 60,0%). A taxa de sobrevivência do grupo G3 foi de 100% ao final do experimento. Esses efeitos moduladores do extrato no processo da artrite parecem não ser dependentes da modulação de marcadores de ativação de linfócitos T, nem de alterações nas subpopulações dessas células (CD4+, CD8+, T regulatórias). Tampouco dependeram da indução de apoptose nos linfócitos esplênicos, conforme avaliado pelas técnicas da anexina V e análise da fragmentação de DNA. Entretanto, aumentos na porcentagem de células B/CD69+ sugerem possível participação destas células no processo de modulação da doença. Analisados conjuntamente, os resultados apresentados sugerem que alguns dos produtos vegetais avaliados podem modular a função de linfócitos B, além de apresentarem importante atividade antiinflamatória em edema de pata induzido por carragenina. Adicionalmente, o extrato AF apresentou ação moduladora na artrite induzida por pristane. Esses resultados fornecem subsídios para o entendimento das atividades biológicas da Alternanthera tenella e para a validação científica do seu uso popularAntiparasitic, antibacterial and antiviral activities in plants of the Alternanthera genus (Amaranthaceae) have been studied. In Brasil, Alternanthera tenella Colla are used in popular medicine as an anti-inflammatory agent. Considering the importance of the immune system in infectious and systemic autoimmune diseases showing intense inflammatory reaction, the objective of this study was to investigate the immunomodulatory activity of A. tenella extracts in BALB/c mice. The plant extracts were also tested in a mineral pristane oil (2,6,10,14-tetramethylpentadecane) induced arthritis model in AIRmax mice, genetically selected for maximal acute inflammatory reactions. Organic solvent crude extracts (ethanol and hexane), aqueous fractions and isolated flavonoids were intraperitoneally inoculated in BALB/c mice immunized or not with sheep red blood cells (SRBC). Immunomodulatory and immunotoxic effects were evaluated by determining body and lymphoid organ weights, splenic cellularity and through functional assays like plaque-forming cells (PFC), antibody anti-SRBC production and carrageenan-induced paw edema. The effects of aqueous extracts on splenic lymphocyte subtypes (CD3, CD4, CD8 and CD19) and apoptosis detection in these cells were further evaluated. The extracts tested did not induce changes in body and organ (spleen, thymus and liver) weights 4 and 14 days after administration. PFC numbers were significantly increased (p<0,05) in SRBC immunized animals treated with 15mg/kg 2-O--L-ramnopiranosilvitexina, a flavonoid isolated from the etanolic (E) crude extract or with the cold aqueous extract (CAE 100 mg/kg) when compared to the controls. The E and CAE extracts induced increased anti-SRBC IgG and IgM circulating antibody titers, suggesting immunostimulatory activity. Aqueous extracts, CAE and hot aqueous extract (HAE), had significant anti-inflammatory activity in the carrageenan paw edema, especially CAE, which showed a dose-related effect (50% and 61% edema inhibition in dosages of 200 mg/kg and 400 mg/kg, respectively). In normal BALB/c mice the extracts did not induce apoptosis or changes in lymphocyte subtypes and T and B activation markers. Based on these results, CAE was selected for tests of modulatory and /or therapeutic activity in a model of pristane induced arthritis in AIRmax mice. Animals (G1, n=15) treated with six doses of CAE (200 mg/kg) before pristane injections showed smaller arthritis incidence when compared to the control positive group receiving pristane only (G4, n=15) (54,4% and 70%, respectively). Percentage of animals showing joint deformities was smaller in G1 (18,2%) in comparison to G4 (30%). The animals receiving extract only (G3, n=14) did not show signs of arthritis. In addition, CAE showed protective activity against ascites development, an inflammatory process that may be induced by the mineral oil. The arthritis incidence index, both in CAE previously treated animals (G1) and in animals treated after pristane injections (G2, n=16), was smaller than in the positive control group (G1=18,2% and G2=6,7% x G4= 50%). It is noteworthy that extract- treated animals, in both groups, also had a higher survival index when compared to the positive control group (G1= 81,9% and G2= 90,8% x G4= 40,2%). The survival index in the G3 group was 100% up to the end of the experiments. The extract modulatory effects in arthritis do not seem to be dependent on the modulation of T lymphocyte activation markers, or on changes in T cells subtypes (CD4+, CD8+, regulatory T cells). Also, they did not depend on apoptosis induction in splenic lymphocytes as evaluated by annexin V and analysis of DNA degradation techniques. However, the percentage increase of B/CD69+ cells suggest their participation in the modulatory process. Together, the results suggest that some of the evaluated plant-derived products may modulate B lymphocyte functions, besides showing important anti-inflammatory activity in carrageenan paw edema. In addition, CAE showed modulatory action in pristane induced arthritis. These results contribute to the understanding of Alternanthera tenella biological activities and provide scientific validation to its popular use.
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Othmane, Omar. "Mecanisme d'action d'un immunomodulateur, le lf 1695 : effets in vitro et in vivo sur les lymphocytes t et sur l'autoimmunite." Limoges, 1986. http://www.theses.fr/1986LIMO0027.
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Crocker, Irene Caroline Evenbly. "Studies on the modulation of phosphodiesterase activity in human T lymphocytes." Thesis, University of Southampton, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284579.
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Al-Mughales, Jamil. "Studies on chemoattractant activity of rheumatoid synovial fluid for human lymphocytes in vitro." Thesis, University of Glasgow, 1996. http://theses.gla.ac.uk/38971/.
Повний текст джерелаАнотація:
The present research was carried out to investigate the chemoattraction activity of rheumatoid and non rheumatoid synovial fluids for human lymphocytes separated from peripheral blood, synovial tissue and synovial fluid. The phenotyping of locomotor cells in response to these fluids was also studied. Established procedures were used to separate lymphocytes from blood, synovial tissue and synovial fluid. The level of the chemotactic factors in the synovial fluid was measured by commercial and in-house developed methods. The inhibitory effect of anti-inflammatory drags on the lymphocyte locomotion was also studied. The chemoattractant activity of synovial fluid for human lymphocytes was investigated using the following methods: i. A Polarization assay which measures the shape change from spherical or round to a polarized shape (i.e from immotile to a motile shape) following stimulation with chemoattractants. ii. Collagen gel invasion, which measures the migration of lymphocytes into collagen gels- containing chemoattractants. Two methods were used for phenotyping the cells responding to the synovial fluids (I) APAAP which allowed the detection of lymphocyte surface markers in stained cytospin preparations, (ii) FACS which allowed the detection of cell surface markers of lymphocytes recovered from collagen gels after collagenase digestion. In addition methods used to measure the levels of chemotactic factors in the synovial fluid, were (I) Commercial single antibody sandwich ELISA kits (R&D) which measured IL-2, IL-8, MIP-1α and MCP-I, (ii) In-house developed multiple antibody sandwich ELISA which measured IL-15 in the fluids. The ability of synovial fluids from patients with rheumatoid (n=35) and other arthritides (n=18) to attract lymphocytes from peripheral blood of normal subjects, from rheumatoid synovia, and from joint fluids, was studied. The majority of synovial fluids from 29 rheumatoid arthritis patients were strongly attractive for blood lymphocytes which had been cultured overnight. Three out of five fluids from OA also attracted lymphocytes but to a lesser extent than RA fluids. In addition four of seven fluids from other inflammatory arthritides also gave high responses Rheumatoid synovial tissue lymphocytes responded to synovial fluids without a requirement for a period of culture. In contrast lymphocytes derived from rheumatoid and other synovial fluids were completely unresponsive to locomotor stimulants. Most of the responding cells from blood mononuclear cell fractions were T lymphocytes and the CD45RO isotype was attracted preferentially. Rheumatoid synovial fluids contained IL-8 , IL-15, MIP-1α and MCP-1 at levels in the nanogram range, sufficient to attract lymphocytes, but levels of IL-2 were too low to exert a chemoattractant effect. In contrast the levels of chemotactic factors in OA fluids were low and these fluids also showed less activity in attracting lymphocytes. The activity of the fluids could not be abolished by treatment with antibodies to IL-8, IL-2, MTP-1α, MCP-1 or IL-15 tested individually, but combinations of these antibodies inhibited most of the activity, suggesting that attraction of lymphocytes by the fluids is due to a combination of attractants. The accumulation of lymphocytes within the synovial fluids was not correlated with any single chemotactic factor mentioned above, suggesting that such accumulation is due to combined chemoattractants. In the present study it was also observed that neutrophils separated from normal blood gave a strong chemotactic response to the synovial fluids. In contrast neutrophils separated from the synovial fluid were immotile, suggesting that these cells had an intrinsic defect or that their locomotion was selectively blocked by synovial fluid chemotactic inhibitors. Moreover there was no correlation between IL-8 or levels of any other single cytokine and the accumulation of these cells in the fluids, indicating the possibility of multiple chemotactic factor involvement. The manipulation of the locomotion activity of lymphocytes in vitro in response to synovial fluid was studied using anti-inflammatory drugs. It was demonstrated that NSAIDs (including Aspirin, Ibuprofen and indomethacin), DMARDs (including gold, D-penicillamine and primaquine) and cytotoxic drugs including rapamycin and cyclophosphamide had no inhibitory effect on lymphocyte locomotion. On the other hand cyclosporin A and Glucocorticosteroids (including dexamethasone, prednisone and prenisolone) showed a significant inhibitory effect.
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Young, Neil T. "Human leucocyte antigen matching and the development of helper and cytotoxic activity by alloreactive lymphocytes." Thesis, Oxford Brookes University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364072.
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Edens, Lucy Marie. "In vitro cytotoxic activity of equine lymphocytes on equine herpesvirus-1 infected allogenic fibroblasts." Thesis, This resource online, 1994. http://scholar.lib.vt.edu/theses/available/etd-12052009-020321/.
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Guipouy, Delphine. "Exploration fonctionnelle de l'activité cytotoxique de lymphocytes T humains en contexte de pathologie et de thérapie." Thesis, Toulouse 3, 2017. http://www.theses.fr/2017TOU30263/document.
Повний текст джерелаАнотація:
Plusieurs populations de cellules immunitaires possèdent une activité cytotoxique permettant l'élimination de cellules altérées. Cette fonction cellulaire est ainsi déterminante dans le contrôle des infections, des processus tumoraux, ou encore des maladies inflammatoires chroniques. Mon projet de thèse se concentre sur des aspects fondamentaux de l'activité lytique de deux populations de lymphocytes T cytotoxiques : les lymphocytes T CD8+ et les lymphocytes T CD4+ régulateurs de type 1. Pour cela, l'exploration des mécanismes de cette activité a été conduite au travers de deux modèles, pathologique et thérapeutique, à différentes échelles biologiques : au niveau de la population ou de la cellule individuelle, mais aussi différentes échelles d'organisations moléculaires : cellulaire et nanoscopique. Nous avons pu démontrer que l'activité de lyse de lymphocytes T CD8+ cytotoxiques face à un excès de cellules cibles est efficace sur des temps prolongés, reposant sur une capacité individuelle fortement hétérogène à effectuer une lyse multiple. L'importance de cette activité de lyse soutenue a été renforcée par l'identification d'un défaut lytique particulièrement prononcé sur le long- terme chez des lymphocytes T CD8+ issus de patients atteints du syndrome de Wiskott-Aldrich. Ce défaut est lié à une activation réduite de l'intégrine LFA-1 et un délai dans la délivrance du coup létal. De plus, la protéine WASP permet de restreindre LFA-1 de haute-affinité en nanoclusters denses ainsi que de permettre l'organisation en un ring de LFA-1 et la localisation des granules lytiques à l'intérieur de celui-ci. Par ailleurs, les lymphocytes T CD4+ régulateurs de type 1 développés dans le cadre d'une thérapie cellulaire (Ovasave(r)) démontrent une capacité de lyse envers les cellules myéloïdes, en complément d'une activité immunosuppressive sur les lymphocytes T conventionnels. Cette activité est mise en place sur du long-terme, jusqu'à atteindre une efficacité optimale, lié à un délai dans la délivrance du coup létal. De manière surprenante, malgré une spécificité pour l'ovalbumine, l'activité cytotoxique semble être indépendante de l'activation du TCR. En outre, la lyse est granzyme-dépendante mais perforine-indépendante. Ainsi ces lymphocytes T thérapeutiques manifestent une activité cytotoxique alternative. Pour conclure, mon projet de thèse a permis de caractériser une activité de lyse soutenue basée sur une capacité individuelle hétérogène. Cette habilité à soutenir une lyse sur du long-terme implique une stabilité de la synapse, où WASP joue notamment un rôle clé pour l'activation et l'organisation de LFA-1. Les lymphocytes T régulateurs thérapeutiques démontrent aussi une activité de lyse soutenue, cependant les acteurs moléculaires sont non conventionnels. De manière générale, une activité de lyse soutenue permettrait de calibrer une réponse cytotoxique prolongée en rapport à la taille de la population cible, ainsi que le partage avec d'autres fonctions cellulaires comme la sécrétion de cytokinesDuring different pathological conditions such as infections, tumoral processes or chronic inflammation diseases, altered cells are eliminated through a cytotoxic activity mediated by several immune cell populations. This cellular function is therefore crucial for carrying out the action of the immune system. My thesis project focuses on fundamental aspects of the lytic activity of two cytotoxic lymphocyte populations: CD8+ T cells and type-1 CD4+ regulatory T cells. To explore the mechanisms of this activity, this study has been driven on two cases, pathological and therapeutic models, at the population and single-cell levels and also at the cellular and nanoscopic scales of the molecular organisation. We have been able to demonstrate that the CD8+ T cell lysis activity against an excess of target cells is effective over prolonged periods, relying on a highly heterogeneous individual capacity to perform multiple lysis. The importance of this sustained cytotoxic activity was reinforced by the identification of a lytic defect, particularly pronounced on a long time period, of CD8+ T cells from Wiskott-Aldrich syndrome patients. This defect is related to a reduced activation of the LFA-1 integrin and delay in the lethal hit delivery. In addition, the WASP protein allows to restrict high affinity LFA-1 to dense nanoclusters as well as the assembly of LFA- 1 ring and the localization of the lytic granules inside this ring. Moreover, type-1 CD4+ regulatory T cells from a cellular therapy (Ovasave(r)) demonstrated a cytotoxic activity toward myeloid cells, additionally to an immunosuppressive activity on conventional T cells. This activity is implemented over long time periods, until reaching optimal efficiency, and is related to a delay in the lethal hit delivery. Surprisingly, despite a specificity for ovalbumin, the cytotoxic activity measured in absence of the antigen suggests a TCR independence. In addition, lysis is not mediated by perforin but is exclusively granzyme-dependent. Thus, these therapeutic T cells exhibit an alternative cytotoxic activity. To conclude, my thesis project permits to characterize a sustained lysis activity relying on a heterogeneous individual capacity. This ability to sustain a lytic activity involves stability of the synapse, where WASP plays a key role towards the activation and organization of LFA-1. The therapeutic regulatory T lymphocytes also demonstrated a sustained cytotoxic activity, however the molecular actors are unconventional. On the whole, sustained lytic activity would be key to the calibration of cytotoxic responses in relation to the size of the target population, as well as sharing with other cellular functions such as cytokine secretion
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Costa, Giulia. "Immune effectors against malaria : deciphering the anti-parasitic activity of γ-delta T lymphocytes". Paris 6, 2009. http://www.theses.fr/2009PA066732.
Повний текст джерелаАнотація:
Malgré des résultats récents encourageants, le développement d’un vaccin anti-paludique est limité par notre connaissance incomplète des mécanismes de l’immunité anti-parasitaire. Les cellules T Vγ9Vdelta2, une population lymphocytaire non-conventionnelle spécifique des primates augmentée et activée au cours de l’infection par Plasmodium falciparum, inhibent in vitro le cycle sanguin du parasite par un mécanisme encore mal compris. Dans un premier temps, nous avons disséqué in vitro ce mécanisme, démontrant que le merozoïte (forme parasitaire invasive) est le seul stade vulnérable dans ce phénomène et que la granulysine, et non la perforine, est un médiateur crucial. Chez les patients primo-infectés, nous avons détecté une proportion élevée de cellules T Vγ9Vdelta2 pourvue de granulysine qui présente une réactivité anti-parasitaire spécifique. Ceci suggère fortement un rôle des cellules TVγ9Vdelta2 dans le contrôle de la charge parasitaire chez ces individus. Dans un deuxième temps, nous avons étudié la modulation de cette activité anti-parasitaire par des anticorps hyper-immuns. Nous montrons que les phosphoantigènes parasitaires induisent l’expression, de CD16 (FcγRIIIa), récepteurs à basse affinité des IgG, sur les cellules T Vγ9Vdelta2 et que le parasite opsonisé par des IgG potentialise l’exocytose de granules cytotoxiques par les cellules T Vγ9Vdelta2 CD16+. Ceci suggère une activité anti-parasitaire renforcée chez les individus exposés. Les cellules T Vγ9Vdelta2 représentent donc un nouvel effecteur anti-palustre pouvant directement contribuer au contrôle de la parasitémie, chez les individus exposés ou nonDespite recent encouraging results, the progress towards an efficient antimalarial vaccine is limited by our incomplete knowledge of immune effectors. Vγ9Vdelta2 T cells, an unconventional T cell subset specific to primates that is activated and expanded during Plasmodium falciparum infections in response to malaria phosphoantigens, inhibit in vitro the growth of parasite blood stages but the underlying mechanisms remain unclear. In a first study, we decipher the whole mechanism by which Vγ9Vdelta2 T cells inhibit in vitro P. Falciparum blood stage development. We demonstrate that the invasive merozoite is the only vulnerable stage in this process in which granulysin, but not perforin, is a crucial mediator. In primary infected patients, we detect high levels of granulysin-containing Vγ9V2 T cells that display specific reactivity towards the parasite, arguing for a role of these cells in the control of parasite density in primary infected patients. In a second study, we investigate the influence of malaria hyper-immune antibodies on the Vγ9Vdelta2 anti-parasitic activity. We show that malaria phosphoantigens induce an up-regulation of CD16 (FcγRIIIa), the low affinity receptor for IgG, on Vγ9Vdelta2T cells. Interestingly, IgG-opsonized infected erythrocytes potentiate the release of cytotoxic granules by CD16+ Vγ9Vdelta2 T cells, suggesting that in exposed individuals opsonizing IgG enhance the anti-parasite activity. Altogether, these results highlight a new mechanism by which Vγ9Vdelta2 T cells might directly contribute to the control of parasite density both in unexposed and exposed individuals
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Perrin, Wolff Mallory. "Etude de l' apoptose induite par les glucocorticoides dans les lymphocytes T : relation de structure-activité et rôle protecteur de l' interleukine-2." Paris 5, 1995. http://www.theses.fr/1995PA05P632.
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Basso, Lilian. "Activité analgésique des lymphocytes T CD4+ dans les maladies inflammatoires chroniques de l'intestin." Toulouse 3, 2015. http://www.theses.fr/2015TOU30036.
Повний текст джерелаАнотація:
La sensation douloureuse est une caractéristique de la réponse inflammatoire qui accompagne les infections par des pathogènes ou les lésions tissulaires. Les médiateurs pro-inflammatoires libérés engendrent un message douloureux via la stimulation des fibres nerveuses sensitives primaires. Ce message douloureux est régulé in situ via la sécrétion d'opioïdes par les lymphocytes T CD4+ effecteurs générés en réponse au pathogène. Les propriétés analgésiques des lymphocytes T CD4+ sont acquises lors de leur activation par l'antigène dans les ganglions drainants via la synthèse de novo d'enképhalines. Les enképhalines sont ensuite libérées par les lymphocytes T CD4+ effecteurs lors de leur arrivée au site de l'inflammation, à la condition d'une nouvelle stimulation par l'antigène. Un défaut de régulation des lymphocytes T CD4+ de la muqueuse intestinale peut conduire au développement de maladies inflammatoires chroniques de l'intestin (MICI). Mes travaux de thèse ont montré chez la souris que les lymphocytes T CD4+ de phénotype Th1 ou Th17, caractéristiques des MICI, que l'on retrouve dans la muqueuse enflammée, produisent des enképhalines. L'utilisation de la technique de distension colorectale m'a permis de mettre en évidence qu'au cours de la phase aiguë de la colite, caractérisée par l'activation des cellules de l'immunité innée, les souris présentent une hypersensibilité viscérale. Celle-ci disparait dans la phase tardive de la maladie, lorsque les lymphocytes T infiltrent la muqueuse enflammée. Cette inhibition de l'hypersensibilité viscérale est dépendante de l'activation des récepteurs opioïdes périphériques par les enképhalines libérées localement par les lymphocytes. L'intensité de l'hypersensibilité viscérale apparait ainsi corrélée au taux d'infiltration de la muqueuse par les lymphocytes T plutôt qu'à l'étendue des dommages tissulaires. Cette observation nous a emmené à concevoir une nouvelle stratégie anti-nociceptive basée sur le recrutement des lymphocytes T dès la phase précoce de la colite. La stratégie que nous avons adoptée pour accélérer le recrutement des lymphocytes T sur le site inflammatoire, était basée sur la mise en place d'une réponse immunitaire secondaire. J'ai montré que l'immunisation préalable des souris permettait, lors d'une seconde exposition à l'antigène in situ, de réduire les douleurs viscérales inflammatoires. Cette stratégie analgésique était efficace dans les deux modèles de douleurs viscérales que j'ai étudiés, la colite induite par le DSS chez la souris, et la cystite interstitielle induite par le cyclophosphamide chez le rat. L'utilisation, lors de mon protocole, de vaccins couramment utilisés en médecine humaine permet d'envisager une application rapide chez l'hommePainful sensation is a hallmark of the inflammatory response induced by the infection by pathogens or tissue damage. Pro-inflammatory mediators released during inflammation directly activate primary sensory neuron to initiate painful message. This painful message is regulated in situ via the secretion of opioids by effectors CD4+ T lymphocytes generated in response to the pathogen. The analgesic properties of the CD4+ T lymphocytes are acquired upon activation by antigen loaded-dendritic cells in the draining lymph nodes via the de novo synthesis of enkephalin. Enkephalins are released by effector CD4+ T lymphocytes upon their arrival at the site of inflammation after new antigen stimulation with the cognate antigen. A defective regulation of CD4 + T cells in the intestinal mucosa can lead to the development of inflammatory bowel disease (IBD). My work shows in mice that Th1 and Th17 effector CD4+ T lymphocytes that are associated with IBD produce enkephalins. Using colorectal distension, I demonstrate that, during the acute phase of colitis, characterized by the activation of innate immune cells, mice exhibit visceral hypersensitivity. This hypersensitivity disappears in the later stages of the disease, when T cells infiltrate the inflamed mucosa. This inhibition of visceral hypersensitivity is dependent on the activation of the peripheral opioid receptors by the local release of enkephalins by CD4+ T cells. The intensity of visceral hypersensitivity appears to correlate with the rate of infiltration of the mucosa by T cells rather than the extent of tissue damage. This observation led us to develop a new anti-nociceptive strategy based on the recruitment of T cells at the early phase of colitis. The strategy that we adopted to accelerate the recruitment of T cells to the site of inflammation, was based on the establishment of a secondary immune response. I showed immunization of mice allowed, during a second exposure of to the antigen in the inflammatory site, reduce inflammatory visceral pain. This analgesic strategy was effective in both models of visceral pain that I have studied, the DSS-induced colitis in mice, and the cyclophosphamide-induced interstitial cystitis in rats. The use, in my protocol, of vaccines commonly used in human medicine allows considering rapid application in humans
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Llaudó, Vallmajor Inés. "P-Glycoprotein functional activity in peripheral blood lymphocytes. Role of immunosuppressants, pharmacogenomics and alloimmune response." Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/134502.
Повний текст джерелаАнотація:
Both immunological and non immunological factors are involved in chronic allograft nephropathy such as donor specific alloreactivity, chronic inflammation and nephrotoxicity induced by anticalcineurinics. Different degrees of nephrotoxicity are related to immunosuppression and to the level of inhibition of the different transporter proteins such as MDR1, MRP1 and MRP2. Those proteins could be subjected to genetic inter-individual variability thus modifying pharmacokinetics parameters. Furthermore, optimal immunosuppressive dose could be predicted by genotype characterization of MDR1, MRP1 or MRP2 genes. Polymorphisms in these genes have been related to immunosuppressive exposure, nephrotoxicity and renal allograft rejection. Those proteins have also been associated to immunological factors. Both MDR1 and MRP1 have been involved in T cell activation and also in dendritic cells (DCs) differentiation, migration and maturation.
It has been hypothesized that ABC transporter proteins play a major role in drug efflux and also may be an underlying factor as an immunomodulator. Considering that many immunosuppressants are substrates and also inhibitors of this ABC transporter proteins, the hypothesis of this doctoral thesis is to evaluate if Pgp activity would participate in lymphocyte activation and if the polymorphisms of this protein in renal transplant recipients with different immunosuppressive regimen could have a functional role in the pharmacokinetics of the immunosuppressants.
The main objective is to study the role of P-glycoprotein as an efflux pump and its contribution in the pharmacokinetics and pharmacogenetics of immunosuppressants. On the other hand, far from the well known role in drug exposition and nephrotoxicity, to improve the knowledge on its function in the alloimmunity responses.
In the first study we compared Pgp expression and efflux activity by measuring Rho123 retention in lymphocytes stored under different conditions to evaluate the potential influence of any of the storing conditions on Pgp expression and functionality. To improve Pgp studies, especially multicentric ones, sampling strategies should be considered in order to optimize the sensitivity and reproducibility of efflux assays. There is no data which compares Pgp activity measured from fresh lymphocytes with cryo-preserved lymphocytes. Moreover, most authors do not specify under which conditions cells are preserved and stored before measuring Pgp activity. Here, we isolated lymphocytes from fresh venous blood from 12 healthy volunteers and four storage conditions of lymphocytes were used.
1) Fresh lymphocytes (Fresh/Non-frozen) (F/NFr);
2) Lymphocytes frozen immediately after the extraction (Fresh/Frozen) (F/Fr);
3) Lymphocytes isolated within 24 hours after the extraction (Non-fresh/Non-frozen) (NF/NFr);
4) And lymphocytes isolated within 24 hours after the extraction and immediately frozen (Non-fresh/Frozen) (NF/Fr).
The objective of the second study was to investigate the association of different ABCB1 polymorphisms (C3435T, G2677T, C1236T and T129C) with Pgp activity and exposure of different immunosuppressive drugs in renal transplant patients from eight different centers. This substudy of pharmacogenomics was part of the Symphony study. The main objective of the Symphony trail was to establish the differences on MPA and its metabolites exposure among the four immunosuppressive groups: MMF in combination with normal or low doses of CsA, low doses of Tac and low doses of SRL. The study was evaluated in seventy patients: CsA (n=30), tacrolimus (n=13) and sirolimus (n=23). For the pharmacokinetic analysis, the AUC0-12 of all immunosuppressants was compared at each time along the follow-up. For this purpose, 11 blood samples were collected for each point: before the first MMF administration of the day and up to 12h post-dose. To perform the study, patients were genotyped for SNPs in ABCB1 gene and moreover, Pgp activity was evaluated in PBMCs using the Rho123 efflux assay.
Considering earlier studies in our group which describes the in vivo impact of the association of Rapa (mTORi) with two calcineurin inhibitors (CsA and Tac) on Pgp function and the involvement of Pgp in this immunosupressor-related renal toxicity, in the next study, we analyzed the activity of Pgp on different T-cell subsets and we studied the effects of the same immunosuppressants in monotherapy and associated with rapamycin. Rho123 uptake, efflux and kinetic of extrusion in CD4+ and CD8+ subsets of peripheral blood mononuclear cells isolated from eight healthy volunteers were measured. We also studied the antigen-specific memory T-cell responses by measuring T-cell proliferation and cytokine secretion using an allogeneic mixed lymphocyte reaction.En la nefropatía crónica del aloinjerto renal (NCT) se implican factores aloinmunes y no aloinmunes tales como la aloreactividad donante específica, inflamación crónica y nefrotoxicidad inducida por los anticalcineurínicos. La nefrotoxicidad varía en función de la combinación de los inmunosupresores. Así mismo, el diferente grado de nefrotoxicidad podría estar relacionado con el grado de inhibición de las diferentes proteínas transportadoras (MDR1, MRP1 y MRP2) que son las responsables de afluir el fármaco hacia el exterior de las células. Considerando la importancia del papel de éstas proteínas, las diferentes variantes genéticas de los genes que las codifican y su función, pueden afectar a la variabilidad interindividual con sus consecuencias en la farmacocinética de muchos fármacos. La monitorización del genotipo de los genes MDR1, MRP1 y MRP2, así como también su función, podría predecir la dosis óptima de los inmunosupresores en receptores de trasplante renal y la dosis inicial que necesita cada paciente individual para obtener la inmunosupresión adecuada. Los polimorfismos de estos genes están relacionados con la exposición al fármaco, la nefrotoxicidad y el rechazo. Estas proteínas también se asocian a factores inmunológicos. Tanto MDR1 como MRP1 juegan un papel importante en la activación de la célula T y también en la diferenciación y maduración de la célula dendrítica. El papel de estas proteínas transportadoras va más allá de una bomba de extrusión ya que se conoce que participan en la respuesta inmune siendo una nueva diana terapéutica para la inmunosupresión. El principal objetivo fue estudiar el rol de la P-Glicoproteína (MDR1/Pgp) tanto como una bomba transportadora de fármacos como su contribución en la farmacocinética y farmacogenética de los inmunosupresores. También se estudió el rol de Pgp en la respuesta aloinmune. En un primer estudio, se comparó la expresión de Pgp y la actividad de eflujo mediante el ensayo de Rodamina (Rho123) en linfocitos de voluntarios sanos guardados en diferentes condiciones para evaluar la influencia que podían tener estas condiciones de almacenaje sobre la expresión y funcionalidad de Pgp. Se puso a punto un método para la medida de actividad de Pgp en linfocitos T, para poder ser aplicada en muestras de linfocitos de pacientes trasplantados renales. Se aislaron linfocitos de la sangre de 12 voluntarios sanos y se evaluó las diferencias de expresión de Pgp a nivel de RNA y proteína, entre linfocitos procesados y guardados en diferentes condiciones de almacenaje. En un segundo objetivo se analizó la asociación de diferentes polimorfismos (SNPs) de Pgp/ABCB1 (C3435T, C1236T, G2677T i T129C) con la actividad de Pgp y la exposición a diferentes fármacos inmunosupresores en 70 pacientes de trasplante renal de diferentes hospitales. En un estudio in vivo donde se describe un modelo de nefrotoxicidad en ratas, se estudió el papel de Pgp en la asociación de Rapa (mTORi) con dos inhibidores de calcineurina (CsA y Tac). A partir de este trabajo, se realizó el siguiente estudio donde se analizó la actividad de Pgp in vitro en diferentes sub-poblaciones de célula T y los efectos de los mismos inmunosupresores solos y asociados con Rapamicina.
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Ralph, Christina. "Modulation of T regulatory activity for cancer therapy." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-t-regulatory-activity-for-cancer-therapy(7e39408d-9790-4a0e-9fa2-b6b065f2265e).html.
Повний текст джерелаАнотація:
Emerging evidence suggests the immune system has a role in preventing cancer, and in advanced cancer evidence of immune dysfunction is widespread. This project focused on cytotoxic T lymphocyte antigen 4 (CTLA4), a key negative regulator of T cell activation found on dedicated regulatory T cells (Treg) and activated T lymphocytes, and asked whether modulation of immune control with anti-CTLA4 blockade led to significant anti-tumour activity. Clinical and laboratory investigation of anti-CTLA4 blockade using tremelimumab in a phase II trial of second-line therapy in advanced oesophageal and gastric adenocarcinomas was combined with an attempt to establish a suitable pre-clinical model based on therapeutic vaccination against the tumour associated antigen (TAA) 5T4.Eighteen patients received tremelimumab. Most drug-related toxicity was mild but there was a single death due to bowel perforation. Four patients had stable disease with clinical benefit; one achieved a partial response after eight cycles (25.4 months) and remains well on study after four years. Markers of regulatory phenotype, forkhead box protein 3 (FoxP3) and CTLA4, doubled transiently in CD4+CD25high lymphocytes in the first month after tremelimumab before returning to baseline. In contrast, CTLA4 increased in CD4+CD25low/negative lymphocytes throughout the cycle of treatment. Post-treatment expanded Treg expressed FoxP3 without interleukin-2 and their defining suppressive function was not abolished despite prolonged anti-CTLA4 blockade. De novo proliferative responses to TAA 5T4 (8 of 18 patients) and carcinoembryonic antigen (CEA; 5 of 15) were detected. Patients with a post-treatment CEA proliferative response had median survival of 17.1 months compared to 4.6 months for non-responders (p=0.002). Baseline interleukin-2 release after T lymphocyte activation was higher in patients with clinical benefit and toxicity. Heterologous mouse 5T4 (m5T4) vaccination showed some evidence of weak therapeutic benefit, but all tumour models investigated had rapidly lethal kinetics. Specific m5T4 immune responses could be detected by serum antibody ELISA and IFN-gamma ELISPOT assays in naive animals but were lower frequency than published responses to h5T4, and were further attenuated in tumour-bearing animals. The addition of anti-CTLA4 blockade did not result in significant augmentation of m5T4 specific immunity after vaccination in non tumour-bearing animals and combination treatment was ineffective as therapy in this autologous model. Results are discussed in the context of emerging immunotherapeutics in melanoma and prostate cancer. In the absence of supportive data from the model system it would not be appropriate to pursue combination heterologous 5T4 vaccine with anti-CTLA4 blockade, but in view of the unusual durability of the best response to tremelimumab, and in vitro evidence of enhanced proliferative responses to relevant TAA, further investigation of drug activity may be warranted in metastatic gastric and oesophageal second-line treatment.
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Hu, Jiancheng. "Regulation of Lsc activity and role in B cell migration and antigen receptor signaling /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
Знайти повний текст джерелаАнотація:
Thesis (Ph.D. in Immunology) -- University of Colorado Denver, 2007.Typescript. Includes bibliographical references (leaves 103-118). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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Jullien, Pascale. "La p561ck dans le lymphocyte T : autophosphorylationde la p56lck et régulation de son activité tyrosine kinase." Paris 11, 1994. http://www.theses.fr/1994PA11T025.
Повний текст джерела
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Secinaro, Michael Anthony. "The Contribution Of Metabolism To The Regulation Of Caspase Activity And Cell Death In T Lymphocytes." ScholarWorks @ UVM, 2019. https://scholarworks.uvm.edu/graddis/1000.
Повний текст джерелаАнотація:
During an immune response, T cell activation is mirrored by a dramatic metabolic shift from oxidative phosphorylation to glycolysis. The upregulation of glycolysis allows the cell to generate the molecules needed to rapidly proliferate and to synthesize effector molecules. The resolution of the T cell response is characterized by equally fast death of most effector T cells. The remaining T cells shift back to oxidative phosphorylation, allowing the cell to survive as a memory T cell. The upregulation of glycolysis and proliferation during the effector phase is paralleled by an increased sensitivity to T cell receptor restimulation-induced cell death (RICD). Whereas cellular metabolism and cell death are important in the proper function and response of T cells, it is not clear how metabolism regulates susceptibility to cell death, nor whether T cell proliferation and contraction are directly connected. The work presented in this dissertation provides a mechanistic link between T cell proliferation and contraction by demonstrating the regulation of caspase-3 activity by the metabolic state of T cells.
In effector T cells, the cytokine interleukin (IL)-2 mediates the upregulation of glycolysis, while IL-15 induces oxidative phosphorylation and a memory-like state. IL-2 is known to sensitize T cells to RICD, while IL-15 reduces RICD and increases survival. This results from the ability of IL-2 and glycolysis to increase caspase-3 activity, whereas IL-15 induces the opposite phenotype. Activation of caspase-3 during glycolysis is mediated through clustering in lipid rafts in the plasma membrane. IL-15 is shown to inactivate caspase-3 through the posttranslational modification of protein glutathionylation, which is mediated by ROS generation in the mitochondria as a by-product of oxidative phosphorylation.
We further observe that glycolysis parallels the reduced activity of the electron transport chain and oxidative phosphorylation, further increasing caspase-3 activity. This is mediated by the decreased expression of electron transport chain complexes and an increase in expression of the negative regulator of complex I, methylation-controlled J protein (MCJ). IL-15 promotes reduced expression of MCJ by its methylation. Similar to IL-15-cultured T cells, MCJ-deficient T cells manifest reduced glycolysis, caspase-3 activity, and RICD. Collectively, these findings demonstrate an adaptation that links metabolism to both cell proliferation and cell death to safeguard that proliferating cells do not escape regulation that could result in autoimmune disease or lymphomas.
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Mamane, Yael. "The regulation of IRF-4 activity in lymphoid cells and involvement in HTLV-I-induced T cell leukomogenesis /." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38229.
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The Human T cell Leukemia Virus (HTLV) is the etiologic agent of adult T cell leukemia (ATL), an aggressive and fatal leukemia of CD4+ T lymphocytes, and is also associated with a neurological demyelinating disease called Tropical Spastic Paraparesis (TSP) or HTLV-I Associated Myelopathies (HAM). The oncogenic potential of HTLV-I resides in the viral Tax oncoprotein, a positive regulator of viral and cellular gene transcription. Interestingly, all HTLV-1 infected cells and Jurkat cells transiently transfected with the HTLV-I Tax gene, express constitutively the Interferon Regulatory Factor-4 (IRF-4), a lymphoid-specific member of the IRF family of transcription factors, indicating that Tax may function as an indirect transactivator the IRF-4 gene. The overexpression of IRF-4 in HTLV-1 infected cells may play a role in viral-mediated cellular transformation and thus in adult T cell leukemia. IRF-4 expression studies revealed its presence in B cells, activated T cell, macrophages and T cells infected with HTLV-I or HTLV-II. In attempt to understand the regulation of IRF-4 expression, promoter analyses were undertaken using genomic footprinting and EMSA. These promoter analyses revealed the involvement of the NF-kappaB and NF-AT family members in IRF-4 regulation. Using IRF-4 as bait in a yeast two hybrid screen, a novel interaction between IRF-4 and the FK506 binding protein 52 (FKBP52), a 59kDa member of the immunophilin family with peptidyl-prolyl isomerase activity (PPIase) as well as chaperone-like functions, was characterized. Inhibition of IRF-4 DNA binding activity as well as transcriptional potential was shown to require functional PPIase of this immunophilin. FKBP52 seems to induce a conformational change in IRF-4 by cis-trans prolyl isomerization which interferes with IRF-4 DNA binding and transactivation. These studies suggest the direct involvement of the immunophilin FKBP52 in the regulation of IRF-4 function by a novel post-translational modification.
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Boué, Jérôme. "Activité analgésique des lymphocytes T CD4+ effecteurs générés au cours de la réponse immunitaire adaptative." Toulouse 3, 2012. http://www.theses.fr/2012TOU30052.
Повний текст джерелаАнотація:
La sensation douloureuse est une caractéristique de la réponse inflammatoire qui accompagne les infections par des pathogènes ou les lésions tissulaires. Un grand nombre de molécules libérées au niveau du site de l'inflammation (cytokines, leukotriènes, neuropeptides, prostaglandines ou protéases) vont permettre la mobilisation des cellules immunitaires et générer un signal douloureux via la stimulation des afférences primaires in situ. Les signaux de douleurs véhiculés par ces afférences primaires peuvent être modulés par les opioïdes endogènes libérés par les cellules immunitaires infiltrant le site inflammatoire. Le système opioïde endogène est constitué d'une vingtaine de neuropeptides répartis en trois familles : les endorphines, les enképhalines et les dynorphines qui se lient respectivement à trois classes de récepteurs opioïdes : MOR, DOR et KOR. Bien que la production d'opioïdes par la plupart des cellules immunitaires ait été décrite, l'analgésie périphérique semble associée à une infiltration par les lymphocytes T. Notre analyse par PCR quantitative des différentes populations de cellules immunitaires murines, a montré que seule l'activation des lymphocytes T (CD4+ et CD8+) et des cellules dendritiques s'accompagne d'une augmentation du niveau d'expression de l'ARNm de la pro-enképhaline. Ce niveau peut atteindre dans les lymphocytes T CD4+ plus de 50% du niveau mesuré dans le cerveau, principal organe producteur d'enképhalines. L'utilisation d'un test de sensibilité à un stimulus mécanique, nous a permis de mettre en évidence le rôle analgésique des opioïdes d'origine lymphocytaire. Les souris Nudes, qui ne possèdent pas de lymphocytes T, sont plus sensibles à la douleur associée à la réponse inflammatoire. Une sensibilité normale est restaurée par l'injection de lymphocytes T CD4+ naïfs spécifiques de l'antigène à l'origine de l'inflammation. La propriété analgésique des lymphocytes T CD4+ est acquise lors de leur activation par l'antigène dans les ganglions drainant le site inflammatoire, via la synthèse de novo d'enképhalines. La production d'enképhalines n'est pas tributaire d'une fonction effectrice particulière des lymphocytes T CD4+ et ne se produit qu'à la condition d'une nouvelle stimulation par l'antigène au niveau du site inflammatoire. L'activité analgésique des lymphocytes T CD4+ est dépendante de la stimulation des récepteurs opioïdes DOR exprimés sur les afférences primaires. La libération d'enképhalines par les lymphocytes T CD4+ effecteurs au niveau du site de l'inflammation pourrait également réduire le flux migratoire des cellules dendritiques vers les ganglions drainants contribuant ainsi à la réduction de l'amplitude de la réponse lymphocytaire TPainful sensation is a hallmark of the inflammatory response induced by pathogens or tissue damage. A large spectrum of molecules released within the inflamed tissue including neuropeptides, prostaglandins, or proteases induces pain by stimulating primary afferents in situ. Painful messages conveyed by primary sensitive fibers are modulated by peripheral endogenous regulatory mechanisms involving local opioïd release by leukocytes infiltrating the inflammatory site. Endogenous opioïd peptides belong to three families: endorphins, enkephalins, and dynorphins, which are derived from protein precursors encoded by three distinct genes: the proopiomelanocortin, the proenkephalin, and the prodynorphin genes, respectively. The biological activities of the opioïd neuropeptides are mediated by three types of seven transmembrane segment G-protein-coupled receptors named µ- (MOR), d- (DOR), and κ- (KOR) opioid receptors. ß-endorphin and enkephalins bind to both MOR and DOR, whereas dynorphin interacts only with KOR. Among immune cells infiltrating the inflammatory site, T lymphocytes have been described to be more efficient to relieve pain. We have quantified the expression level of mRNA encoding for all three opioïd precursors in dendritic cells, CD4+ and CD8+ T lymphocytes, B lymphocytes and macrophages in mice. We found that cell activation up-regulates proenkephalin mRNA level only in dendritic cells and CD4+ T lymphocytes. In activated CD4+ T lymphocytes, proenkephalin mRNA level were the highest, reaching more than 50% of that measured in brain, the main enkephalins producing organ. The role of T cell-mediated immunity in regulation of inflammatory pain was first appreciated by comparing nociceptive response to mechanical stimuli. T cell-deficient nude mice are more sensitive to inflammatory pain than wild-type mice. Normal sensitivity is restored by injection of naïve CD4+ T lymphocytes specific to the antigen responsible for inflammation. Analgesic property of CD4+ T lymphocytes is acquired in response to their specific antigen within draining lymph nodes, by de novo synthesis of enkephalins. Enkephalins production is irrespective of effector CD4+ T cell functions and is dependent upon specific antigen recognition at the inflammatory site. CD4+ T cell-induced analgesia is dependent on DOR activation on primary afferents. Enkephalins release by effectors CD4+ T cells within inflammatory site could also decrease dendritic cells migration to draining lymph nodes that contribute to T lymphocytes response reduction
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Nicolas-Gaulard, Isabelle. "Activité immunomodulatrice d'une protéine, l'hypodermine A, sur les cellules sanguines mononucléées des bovins." Paris 12, 1995. http://www.theses.fr/1995PA120031.
Повний текст джерелаАнотація:
Parmi les grandes maladies parasitaires qui affectent le cheptel bovin francais, l'hypodermose est responsable de pertes economiques importantes. Le premier stade larvaire de l'insecte responsable de cette parasitose provoque une desorganisation des systemes de defense de l'hote. Ces defaillances sont causees par les secretions larvaires et principalement par l'hypodermine a (ha). L'objet de ces travaux est l'etude de l'activite immunomodulatrice de l'ha sur les cellules sanguines mononucleees des bovins. L'ha inhibe la proliferation des lymphocytes apres stimulation par une lectine mitogene ou par un agent chimique et agit sur la phase precoce de l'activation cellulaire. De plus, l'indometacine, qui inhibe la synthese des prostaglandines, restaure la reponse proliferative des pbmc. La production en pge#2 est augmentee par l'ha dans les cultures de pbmc ou de monocytes. Les concentrations en pge#2 equivalentes a celles dosees dans les cultures en presence d'ha sont inhibitrices de la reponse proliferative a la phytohaemagglutinine. L'ha agirait donc sur la diminution de la reponse des pbmc par une voie dependante des prostaglandines. L'ha induit une baisse de la production d'il2 et beaucoup moins importante de l'ifn dans ces cultures stimulees par la phytohaemagglutinine. Une restauration de la proliferation des lymphocytes est observee par adjonction de surnageant enrichi en il2. La fonction accessoire des monocytes et la production de no, qui sont impliquees dans la proliferation des lymphocytes, sont inhibees par l'ha. L'ha module egalement l'expression de differents marqueurs a leur surface. Tous ces mecanismes decrits in vitro pourraient expliquer les phenomenes d'echappement du parasite au systeme immunitaire du bovin
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Peyron, Jean-Francois. "Etude du role des reactions de phosphorylation au cours de l'activation du lymphocyte t : stimulation precoce d'une activite serine kinase et d'une activite tyrosine kinase." Nice, 1987. http://www.theses.fr/1987NICE4162.
Повний текст джерелаАнотація:
L'activation des lymphocytes t par le recepteur de l'antigene cd3-ti entraine la stimulation de deux activites kinase independantes: une activite serine kinase qui conduit a la phosphorylation de 2 proteines cytosoliques (pp21 et pp23); une activite tyrosine kinase qui a pour substrats au moins huit proteines cellulaires, cette activite est regulee negativement par l'activation de la proteine kinase c et par le taux amp cyclique intracellulaire
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Girmes-Grieco, Nicolin Katleen. "Soy Isoflavone Supplementation Does Not Alter Distribution of Circulating Lymphocytes or Natural Killer Cell Activity in Postmenopausal Women." Thesis, Virginia Tech, 2001. http://hdl.handle.net/10919/33130.
Повний текст джерелаАнотація:
A growing body of evidence has demonstrated that soy isoflavone consumption may protect against the development of various chronic diseases. This defense could be linked to isoflavone-induced alterations in immune function. However, to date, no study has examined the effect of soy isoflavone supplementation on human immunity in vivo. Establishing whether isoflavones affect immunity in aging adults is particularly relevant since compromised immune function has been observed in this population. Therefore, the purpose of this double-blind, placebo-controlled, 4-wk intervention trial was to investigate whether supplementation with soy isoflavones influenced the distribution and/or function of specific lymphocytes in postmenopausal women. Healthy postmenopausal women (50-69 y), who were not using hormone replacement therapy, were randomly divided into 2 treatment groups. The experimental group (n=9) consumed two-50 mg soy isoflavone tablets/d for 4 wk, while the control group (n=9) received placebo tablets. Fasting blood samples were drawn at baseline and on d 28 to assess distribution of T-helper cells (CD3+CD4+), T-cytotoxic cells (CD3+CD8+), total T lymphocytes (CD3+), B lymphocytes (CD19+) and natural killer (NK) cells (CD16+CD56+) via flow cytometry. Cytotoxicity of NK cells was quantified based on lactate dehydrogenase release of lysed K562 cancer cells following co-culture with NK cells from subjects. Analysis of plasma isoflavone concentrations by HPLC demonstrated a significant increase (p<0.005) in plasma genistein concentration in the experimental group after 4 wk of supplementation. However, there was no alteration in lymphocyte distribution or NK cell activity in response to isoflavone supplementation, suggesting that short-term soy isoflavone supplementation does not alter these parameters of immunity in healthy postmenopausal women.Master of Science
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Malinvaud-Lasfargues, Agnès. "Détermination de structures impliquées dans les activités immunologiques des lipopolysaccharides, par l'utilisation de composés synthétiques modèles." Paris 11, 1988. http://www.theses.fr/1988PA112204.
Повний текст джерелаАнотація:
Les endotoxines (LPS) isolées des bactéries à gram-négatif présentent, spectre de réponses chez les cellules du système immunitaire, dont la prolif6ration des lymphocytes B et l'activation des macrophages, Les activités de glycolipides et de sucres préparés par synthèse, et structurellement reliés aux régions (lipide A) et polysaccharidique (PS) du LPS, ont été comparées à celles induite par l'endotoxine de Bordetella pertussis, et par les fragments en dérivant. L'induction de la prolifération des cellules B par des monosaccharides requiert la présence d'un groupe hydroxyle non substituté en position 3, et en une autre position. L'activation des macrophages in vitro pour l'expression d'une activité cytostatique à l'encontre de cellules tumorales, et pour la production d'interleukine-1 (IL-1) et de facteur nécrosant les tumeurs (TNF), a été également étudiée. Le monosaccharide mimant l'extrémité réductrice du lipide A possède quatre critères identifiés comme étant nécessaires pour induire une activité cytostatique chez les macrophages. Les deux régions du LPS de B pertussis (PS et lipide A) sont capables d'induire la synthèse d'IL-1. Seul un des glycolipides de synthèse (M9) induit de Manière plus efficace que le lipide A et le LPS la sécrétion d'IL-1, alors que les dérivés synthétiques de l'acide 3-déoxy-D-manno-2-octulosonique (KDO) n’induisent pas la production d'IL-1. Les structures requises pour l'induction de la production de TNF sont différentes de celles requises pour l'activité cytostatique, l'analogue de l’extrémité non réductrice du lipide A, actif dans ce premier test, est inactif dans le dernierEndotoxins (LPS) isolated from gram-negative bacteria elicit a broad panel of responses in cells of the immune system, including B lymphocyte proliferation and macrophage activation. Activities of glycolipids and carbohydrates prepared by synthesis, and structurally related to the hydrophobic (lipid A) and to the polysaccharide (PS) region of LPS were compared with those induced by Bordetella pertussis endotoxin and by fragments derived therefrom. Induction of B-cell proliferation by the monosaccharide-derived glycolipids requires the presence of unsubstitued hydroxyl groups at position 3, and at least one other position. Activation of macrophages in vitro for expression of cytostatic activity against tumor cells and for the production of Interleukin-1 IL-1) and Tumor Necrosis Factor (TNF), was also examined. The monosaccharide resembling the reducing unit of lipid A fulfills four criteria identified as necessary to induce macrophage-dependent cytostasis. As regards IL-1 production, both isolated regions of B. Pertussis LPS (PS and lipid A) were able to induce IL-1 synthesis. Only one (among 15) synthetic glycolipid (M9) induced IL-1. Derivatives of 3-deoxy-D-manno-2-octulo sonic acid (KDO) failed to induce IL-1 production. The substructures required for the induction of TNF production did not overlap with those triggering a cytostatic activity either, since the analog of the non reducing moiety of lipid A, active in the former test, is inactive in the latter
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Hayden, Rachel Elizabeth. "In Vitro Studies of the Anti-Leukaemic Activity of Bezafibrate and Medroxyprogesterone Acetate Against Chronic Lymphocytic Leukaemia." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/769/.
Повний текст джерелаАнотація:
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the western world, and continues to have very low cure rates. The bulk of the tumour cells are non-cycling peripheral cells that accumulate from a minority of dividing cells within proliferation centres (PCs), located the lymph nodes (LN) and spleen. The PCs are rich in activated T helper (TH) cells that express CD40L and secrete IL-4. Like normal B cells, CLL cells interact with TH via their expression of CD40 and receive signals from IL4. This stimulation provides the signal for B cells to divide, as well as protecting them from apoptotic stimuli. Consequently, many current therapies are unable to sufficiently target the cells in the PC, resulting in therapy resistance, residual disease (RD) and relapse. In addition, most therapies have associated toxicities, restricting their use to younger, fitter patients. Thus, there is an urgent need for new therapies with low toxicity, especially for older patients. New drug discovery is time consuming and expensive. Redeployment of existing drugs is one way to potentially combat this issue. The lipid lowering drug Bezafibrate (BEZ) and the sex steroid, medroxyprogesterone acetate (MPA) have been shown to have anti-leukaemic properties in other settings. In this study the in vitro efficacy of BEZ and MPA on resting CLL cells (representing resting cells in the periphery) and when stimulated to proliferate by CD40L (representing cells in the PCs) have been investigated. Both BEZ and MPA exerted pro-apoptotic actions against resting CLL cells and reduced CD40L stimulated proliferation. These actions were increased when both agents were combined and demonstrated selectivity against CLL cells compared to normal peripheral blood mononuclear cells. Combined BEZ+MPA, was as effective as the commonly used chemotherapeutic chlorambucil, with the combination of all 3 agents exerting the greatest effects. However none of the combinations induced apoptosis of CLL cells protected by CD40L. Investigations into the possible mechanisms of drug action revealed that MPA was unlikely to be working either by steroid receptors or by inhibition of the enzyme AKR1C3 and the mechanism remains unknown. BEZ alone and in the presence of MPA induced the production of prostaglandin D2 (PGD2) and exogenously applied PGD2 was found to exert apoptosis in a similar manner to BEZ. Both BEZ and MPA generated reactive oxygen species (ROS) in both culture settings and the combination was more effective than either drug alone. In the absence of CD40L, mitochondrial superoxide (MSO) was also produced but not in CD40L stimulated cells. This finding suggested that CD40L is able to prevent or protect against MSO production and, consequently, apoptosis. Attempts at overcoming this effect revealed that the plant derived compound lycorine exerted minimal effects alone but, when combined with BEZ+MPA, reinstated the induction of MSO and recapitulated BEZ+MPA induced apoptosis despite the continual presence of CD40L. In contrast, the reported ability of dasatinib to overcome CD40L mediated fluadarabine resistance was discovered to be to be unfounded.
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Durrieu, Christèle. "Activité immunomodulatrice d'extraits hydrosolubles de fromages affinés de la région Rhône-Alpes : développement d'une méthodologie et évaluation in vitro." Lyon 1, 2005. http://www.theses.fr/2005LYO10171.
Повний текст джерелаАнотація:
L'activité immunomodulatrice d'extraits hydrosolubles de 4 fromages affinés à pâte pressée (Emmental, Beaufort, Abondance, Tomme de Savoie) a été évaluée par la mise en œuvre d'une méthodologie in vitro qui repose sur l'utilisation de 2 lignées cellulaires (hybridomes et lymphocytes T humains) et l'optimisation de 2 tests de criblage in vitro permettant d'évaluer l'impact des extraits fromagers sur la synthèse d'ADN et l'activité métabolique des cellules. Les extraits de Tomme de Savoie et d'Abondance ont présenté l'activité immunomodulatrice in vitro la plus importante. L'extrait d'Abondance a conduit à l'amélioration de la densité cellulaire maximale des 2 lignées cellulaires et à l'augmentation de 50% de la production d'anticorps par les hydridomes. Enfin, le fractionnement de cet extrait a permis de suggérer que les peptides sont en partie responsables de l'activité immunomodulatrice et d'identifier un fragment peptidique de la caséine b (f29-39) dont l'activité reste à confirmer
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Cebo, Christelle. "Activité lectinique des cytokines humaines : implications dans les voies de transduction lymphocytaires et modélisation de l'interaction cytokine-ligand." Lille 1, 2001. https://pepite-depot.univ-lille.fr/RESTREINT/Th_Num/2001/50376-2001-145.pdf.
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Simões, Catarina Morgado. "Frequency and functional activity of Vδ1 T cells in chronic lymphocytic leukaemia and in monocional B cell lymphocytosis". Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/22710.
Повний текст джерелаАнотація:
Mestrado em Bioquímica - Bioquímica ClínicaA leucemia linfocítica crónica (LLC) é uma doença linfoproliferativa crónica de células B caracterizada pela proliferação descontrolada de linfócitos B patológicos. É uma doença de curso geralmente indolente, mas que pode em alguns casos progredir rapidamente e necessitar de tratamento. Com vista a melhorar o prognóstico destes doentes, imunoterapias baseadas em células T têm vindo a ser desenvolvidas, com especial interesse numa subpopulação minoritária dos linfócitos T: células T γδ. Estas células representam, normalmente, menos de 10% dos linfócitos T circulantes, apresentando características distintas dos linfócitos αβ, o que lhes confere vantagem quando selecionadas para terapia celular. Dentro deste grupo de células, os linfócitos T Vδ1 parecem exibir atividade citotóxica contra células B de LLC, e como tal podem vir a ser utilizadas em protocolos de imunoterapia anti-tumoral. No entanto, o comportamento destas células in vivo é francamente desconhecido tanto em situações de normalidade, como de doença. O objetivo deste projeto foi estudar a frequência das células Vδ1 em sangue periférico e avaliar, através de estudos imunofenotípicos, a sua atividade efetora e citotóxica (expressão de CD27, CD69 e granzima B) em casos de LLC, de linfocitoses B monoclonais (LBM) e num grupo controlo. Os resultados mostraram uma expansão do compartimento efetor em todas as subpopulações de linfócitos T, particularmente nas células TCD8+ e nas células T Vδ1, o que se correlacionou com um aumento destas células a expressar granzima B desde o grupo controlo até ao grupo de LLC com estádio mais avançado da doença. A percentagem de células a expressar o marcador de ativação CD69 foi marcadamente mais alta nas células T Vδ1, mas no grupo controlo. Assim, os resultados obtidos sugerem que as células TVδ1 parecem apresentar um fenótipo efetor citotóxico, com características semelhantes às células TCD8+ e restantes subpopulações de células T γδ, o que parece evidenciar que conjuntamente com outras células, as células TVδ1 podem contribuir para uma atividade na resposta antitumoral contra células B de LLC.
Chronic lymphocytic leukaemia (CLL) is a B-cell chronic lymphoproliferative disease characterized by an uncontrolled proliferation of pathological B lymphocytes. This disease is normally of indolent progression, but it may, in some cases, progress rapidly and require treatment. In order to improve the prognosis of these patients, T-cell based immunotherapies have been developed, with special interest in a minor subpopulation of T lymphocytes: γδ T cells. These cells represent, normally, less than 10% of circulating T lymphocytes and exhibit distinct characteristics comparing to αβ T lymphocytes providing them with advantages when selected for T cell therapy. Within this group, Vδ1 T lymphocytes seem to display cytotoxic activity against B cells from CLL, conferring to these cells the ability to be used in antitumoral immunotherapies. However, the behaviour of these cells in vivo is frankly unknown in both normal and disease situations. The objective of this project was to study the frequency of Vδ1 T cells on peripheral blood and to evaluate, through immunophenotypic studies, their effector and cytotoxic activity (expression of CD27, CD69 and granzyme B) in CLL, monoclonal B cell lymphocytosis (MBL) and controls. Our results disclosed an expansion of effector compartment in all subpopulations of T lymphocytes, particularly for CD8+ T cells and Vδ1 T cells, which correlated with an increase in these cells expressing granzyme B from control group to advanced stages of CLL. CD69 expression was markedly higher in Vδ1 T cells, in the control group. In conclusion, the results obtained suggest that Vδ1 T cells appear to present an effector cytotoxic phenotype, with similar characteristics to CD8 + T cells and the remaining γδ T cells, which might point to a contribution to an antitumor response against CLL cells, mediated by the interplay between these cells.
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Pernollet, Martine. "Modification de l'antigène toxine tétanique par des radicaux libres oxygénés et par des protéines à activité peptidyl-prolyl cis-trans isomérase : influence sur sa présentation à des lymphocytes T spécifiques." Université Joseph Fourier (Grenoble ; 1971-2015), 1994. http://www.theses.fr/1994GRE10238.
Повний текст джерелаАнотація:
L'influence du radical libre oxygene, le radical hydroxyle (oh) et des proteines a activite peptidyl-prolyl cis-trans isomerase sur le traitement de l'antigene toxine tetanique par des cellules presentatrices d'antigenes (lymphocytes b) a ete etudiee. En ce qui concerne le radical hydroxyle, sa production par des cellules de type macrophagique a ete reproduite a l'aide d'un systeme chimique. La toxine tetanique traitee par le radical oh subit un changement de conformation, et des liaisons bityrosine intramoleculaires resistantes a la proteolyse sont formees. La toxine ainsi modifiee est plus resistante a la proteolyse in vitro par des fractions endosomales isolees des cellules presentatrices. Cette diminution de proteolyse est correlee a une meilleure presentation par des cellules presentatrices fixees, a des lymphocytes t lorsque cet antigene est pre-proteolyse in vitro par des fractions endosomales. Ainsi, le radical oh favorise la presentation des epitopes de la toxine en les protegeant contre une proteolyse trop importante. La production du radical oh par un autre systeme chimique a permis de montrer l'existence d'un site de fixation pour le zinc a l'interieur de la chaine legere de la toxine, au niveau d'un epitope t. En ce qui concerne les activites peptidyl-prolyl cis-trans isomerases (ppiase), celles-ci ont pu etre mises en evidence dans les fractions endosomales de cellules presentatrices. L'addition a ces fractions endosomales de proteines a activite ppiase telles que la cyclophiline ou la fkbp augmente la proteolyse de la toxine tetanique. Il reste a tester les consequences de cet effet sur la presentation de cette derniere a des lymphocytes t. Un autre point de ce travail a ete la mise en evidence de la phosphorylation in vitro de la cyclophiline par la proteine kinase c purifiee. L'etude des consequences de cette phosphorylation sur l'activite ppiase de la cyclophiline est en cours
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Gillis, L. Jane. "Expression and recombinase activity of RAG 1 and two splice variants of RAG 2 in mature human primary tonsilar B lymphocytes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0004/MQ46022.pdf.
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Zhou, Yuetao [Verfasser], and Florian [Akademischer Betreuer] Lang. "DJ-1 sensitivity and functional role of Na +/H + exchanger 1 (NHE1) activity in T lymphocytes / Yuetao Zhou ; Betreuer: Florian Lang." Tübingen : Universitätsbibliothek Tübingen, 2016. http://d-nb.info/1165235781/34.
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Lecron, Jean-Claude. "Caractérisation biologique et physicochimique d'un facteur "Prothymocyte Differentiating Activity" (PTDA) capable de promouvoir la différenciation et l'activation de lymphocytes T humains." Grenoble 2 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb37615119g.
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