Дисертації з теми "Innate lymphocyte cells"
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Esplin, Brandt L. "Replenishment of innate immune system in health and disease." Oklahoma City : [s.n.], 2009.
Знайти повний текст джерелаNarayan, Kavitha. "The Function of Innate γδ T Cell Subsets is Molecularly Programmed in the Thymus in Three Stages: A Dissertation". eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/527.
Повний текст джерелаThomas, Katja, Tony Sehr, Undine Proschmann, Francisco Alejandro Rodriguez-Leal, Rocco Haase, and Tjalf Ziemssen. "Fingolimod additionally acts as immunomodulator focused on the innate immune system beyond its prominent effects on lymphocyte recirculation." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-227035.
Повний текст джерелаSalem, Fatouma. "Identification de biomarqueurs prédictifs de la survenue d'une arthrite chez le patients atteints de maladie inflammatoire chronique de l'intestin (MICI)." Thesis, Université de Lorraine, 2021. http://www.theses.fr/2021LORR0341.
Повний текст джерелаSeveral pieces of evidence are in favor of a link between joint and gut inflammation including the high percentage of inflammatory bowel diseases (IBD) patients developing axial spondyloarthropathy (SpA) and the clinical success of cytokines-blocking therapies in both diseases. However, whether such co-occurrence is causative rather than correlative remains an open question. From a pathophysiological point of view, the lamina propria (lp) in the intestine is enriched in cells of type 3 immunity including TH17 cells and type 3 innate lymphoid cells (ILC3s). These cells play a homeostatic role in intestinal defense by acting as a firewall against extracellular pathogens but can lead to gut inflammation and possibly auto-immunity in case of excessive activation. Their IL-23-driven differentiation depends on the transcription factor RORγt which is repressed by the nuclear receptor PPARγ. As a consequence, PPARγ has emerged as a master regulator of the IL-17/TH17-ILC3 pathway and as it is also able to modulate the release of antimicrobial peptides, it is a possible key interactor between fecal microbiota and gut mucosa by regulating the local immune response and microbiota composition. To investigate the regulatory role of PPARγ in gut inflammation, independently from its overall metabolic impact on adipogenesis, we generated mice that are deficient for PPARγ in immune cells, namely PPARγ invalidation in RORγt expressing cells (RORγtcre+ PPARγfl/fl ). Using the DSS (dextran- sodium sulphate) colitis model, we failed to demonstrate any worsening of the disease nor increase in immune type 3 cell populations in the lp of PPARγ deficient mice. Such lack of effect was not modified by preliminary cell depletion with anti-CD3 antibody and was also observed in the expectedly more ILC3-dependent colitis model induced by anti-CD40 antibody injection. These data do not support a major role of PPARγ in type 3 immune cells during gut inflammation or alternatively that the underlying pathomechanisms poorly depend on type 3 immunity in these animal models. To search for biomarkers characteristic of axial SpA occurrence in IBD patients, we build the Floracrohn cohort to compare patients with Crohn's disease (CD) without joint inflammation, patients with axial SpA (SpA) without gut inflammation, patients with CD having developed axial SpA (CD+SpA) and non-diseased patients. Patients groups were mainly treated with anti-TNFα and were comparable in terms of smoking consumption. We confirmed that CD+SpA patients had more severe diseases and showed that bacterial microbiota was strongly influenced by CD over SpA with some emerging bacterial groups. In contrast, gut fungome was strongly influenced by SpA over CD with a decrease of certain fungi strain as a possible emerging signature of SpA in IBD patients. No distinct polymorphisms frequencies were found amongst the 23 studied in the IL-17/IL-23 pathways. The search for a specific fungome signature may be helpful to identify CD patients at risk of developing axial SpA and this could be completed by cytokines profiling currently under investigation
Shekhar, Sudhanshu. "A study on the role of lung dendritic cells and their interaction with innate lymphocytes in host defense against a bacterial lung infection." Karger, 2015. http://hdl.handle.net/1993/30622.
Повний текст джерелаOctober 2015
Prince, Amanda L. "The Role of Inducible T Cell Kinase (Itk) in the Development of Innate T Cells and in the Formation of Protective Memory Responses: A Dissertation." eScholarship@UMMS, 2013. https://escholarship.umassmed.edu/gsbs_diss/660.
Повний текст джерелаPrince, Amanda L. "The Role of Inducible T Cell Kinase (Itk) in the Development of Innate T Cells and in the Formation of Protective Memory Responses: A Dissertation." eScholarship@UMMS, 2002. http://escholarship.umassmed.edu/gsbs_diss/660.
Повний текст джерелаDubois, Natasha. "Caractérisation de la réponse immune induite par un adjuvant comprenant un agoniste du TLR4 dans des modèles murins." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS131/document.
Повний текст джерелаIn 2014 tuberculosis (TB) surpassed HIV as the leading cause of death by an infectious disease worldwide emphasizing the urgent need to develop a more effective vaccine against this airborne disease. The Infectious Disease Research Institute (IDRI) TB candidate vaccine ID93/GLA-SE is currently undergoing a Phase IIa clinical trial and has shown promising preclinical and clinical results. In murine models of TB this vaccine drives a strong CD4 TH1 response, which is thought to be important for protection against TB, and an IgG2c skewed B cell response. However, little is known about the cellular and molecular events that drive GLA-SE adjuvanticity.To that end, the main objective of my thesis was to elucidate the key mechanisms that connect innate and adaptive immune responses elicited by this adjuvant in the murine model. A secondary objective was to evaluate the possibility of using ID93/GLA-SE as adjunct therapy to existing antibiotic treatments to reduce relapse rates after TB treatment.Collectively the results obtained during this research project and thesis broaden our knowledge and our current understanding of the mechanisms involved in the adaptive immune response induced by GLA-SE and show the capacity of ID93/GLA-SE to be used as a therapeutic vaccine against TB to reduce post-therapeutic relapse rates
Felices, Martin. "The Role of TEC Family Kinases in Innate T Cell Development and Function: a Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/373.
Повний текст джерелаVerrier, Thomas. "Function and plasticity of NKp46 expressing innate lymphoid cells." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC173/document.
Повний текст джерелаGroup 3 Innate Lymphoid cells (ILC3) actively maintain mucosal homeostasis through the production of Interleukin-22 (IL-22). ILC3 encompass 2 major populations, LTi (« Lymphoid Tissue inducer »), characterized by the expression of the chemokine receptor CCR6, and ILC3 that express the transcription factor T-bet, which include a population expressing the surface marker NKp46, a receptor originally used to identify group 1 ILC (ILC1). ILC1 plays a major role in the defense against intracellular pathogens and anti-tumoral responses. Three major ILC1 populations have been identified: the cytotoxic lymphocytes « Natural Killer » (NK or ILC1b), which largely rely for on the transcription factor Eomes their generation and express the integrin CD49b; hepatic and intestinal ILC1 that depends on the T-bet transcription factor and express CD49a (ILC1a); and a population that expresses CD49a and CD49b (ILC1ab) and populates the salivary gland and the uterus, which is independent of the transcription factor Nfil3. My work aimed to understand the biology of NKp46 expressing ILC, as well as factor involved in their development, maturation and function. The major part of my work focuses on NKp46+ ILC3. First, we demonstrate a major role for the chemokine receptor CXCR6 in their localisation in the lamina propria villi (Satoh-Takayama et al. 2014). Second, I showed that NKp46+ ILC3 could lose NKp46 expression (Verrier et al. 2016). Induced by TGFβ, this loss of expression was associated with higher IL-22 production and by the acquisition of markers identifying LTi (CCR6, MHC-II), demonstrating NKp46+ ILC3 plasticity. Finally, in collaboration with Rachel Golub’s group, we confirmed a putative role for Notch-signaling in this plasticity (Chea et al. 2016). In this manuscript, I will discuss the development and the heterogeneity of ILC3, ILC1a, ILC1b and ILC1ab. All the results I generated support a dynamic vision of ILC biology, which reflects how they adapt in response to environmental cues. By characterizing the different actors involved in this dynamic process, my work could be used to design therapies aiming at controlling the equilibrium between these different populations in diverse pathologies such as cancer, viral infection, or intestinal diseases
Thierry, Antoine. "Implication de l'immunité innée au cours des phénomènes d'ischémie-reperfusion : rôle de l'axe IL-33/lymphocytes iNKT." Thesis, Poitiers, 2013. http://www.theses.fr/2013POIT1409.
Повний текст джерелаIschemia reperfusion injury (IRI) is inherent to the transplantation process and its severity is correlated with graft outcome. The pathophysiological mechanisms of these lesions are still poorly understood. The endogenous molecules high mobility group box 1 (HMGB1) and interleukin (IL)-33 have been identified as alarmins, capable of initiating the inflammatory response and thereby to be potentially useful biomarkers in IRI. The pig is a relevant preclinical model to investigate IRI. Because iNKT cells are a component of innate immunity implicated in IRI, we first identified and characterized these cells in pig peripheral blood and showed that they are targeted by IL-33. We then addressed the role of alarmins as innate immune mediators in IRI following human kidney transplantation. Urinary HMGB1 and IL-33 levels were increased early after reperfusion, whereas increased serum and urinary IL-33 were positively correlated with cold ischemia time. In vitro, human umbilical vein endothelial cells subjected to hypoxia conditions released both HMGB-1 and IL-33, while only the latter was further increased upon subsequent re-oxygenation. Moreover we showed that peripheral leukocytes from recipients are potentially targeted by both HMGB1 and IL-33, as attested by increased transcription of their respective receptors. Consistent with this view, we found that iNKT cells that are targeted by IL-33 but not by HMGB1 were activated as soon as 1 hour post-transplantation. Altogether, these results are in keeping with a potential role of IL-33 as an innate-immune mediator during kidney IRI in humans
Malhotra, Nidhi. "Distinct Gene Circuits Control the Differentiation of Innate Versus Adaptive IL-17 Producing T Cells: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/579.
Повний текст джерелаKiaf, Badr. "Les lymphocytes MAIT induisent l'inflammation, la dysbiose et le diabète de type 2 au cours de l'obésité." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC314/document.
Повний текст джерелаObesity and type 2 diabetes are associated with low-grade chronic inflammation. Immune cells are recruited and activated in several tissues, including adipose tissue, thereby contributing to insulin-resistance and diabetes. Recent studies described gut microbiota dysbiosis as a consequence as well as a driver of obesity and type 2 diabetes. Mucosaassociated invariant T cells (MAIT) are innate-like T cells expressing a semi-invariant T-cell receptor restricted by the non-classical MHC class I molecule MR1 presenting bacterial ligands. In obese/T2D patients MAIT cells in blood and adipose tissue exhibit a pro-inflammatory profile. In the present study, we show that during high fat diet-induced obesity MAIT cells produce inflammatory cytokines in adipose tissue and the ileum and induce inflammation in these tissues by modifying other immune cell populations (i.e. macrophages, CD8 Taß cells, NK cells, LTreg, eosinophils and ILC2 in the adipose tissue and ILC2, ILC3 and LTreg in the ileum). These changes impair the function of both tissues leading to insulin resistance, glucose intolerance, impaired lipid metabolism and increased gut permeability. MAIT cells also impact gut microbiota dysbiosis during obesity and microbiota transfer experiments highlight a bidirectional crosstalk between MAIT cells and the gut microbiota leading to inflammation and gut leakage. Altogether these results reveal the major role of MAIT cells in promoting the development of type 2 diabetes during obesity
Lim, Ai Ing. "Cytokine control of human innate lymphoid cell development and function." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC272/document.
Повний текст джерелаInnate lymphoid cells (ILC) represent a novel family of hematopoietic effectors that serve essential roles in early immune response by rapid cytokines production. Three distinct groups of ILC subsets have been described. Group 1 ILC include cytotoxic natural killer (NK) cells and other type-1 cytokines (IFN-? and TNF-?) producing cells that regulated by T-BET. Group 2 ILC (ILC2) express GATA-3 and ROR?, secrete type-2 cytokines, IL-5 and IL-13. Group 3 ILC (ILC3) utilize ROR?t to drive production of the TH17-associated cytokines, IL-17 and/or IL-22. In this thesis, I have performed series of experiments to uncover the developmental pathway and function of human ILC that may allow us to harness ILC in diverse clinical settings. First, I analyzed the phenotypic and functional heterogeneity of human peripheral blood ILC2. I found human IL-13+ ILC2 can acquire the capacity to produce IFN-?, thereby generating ÔplasticÕ ILC2. ILC2 cultures demonstrated that IFN-?+ ILC2 clones could be derived and were stably associated with increased T-BET expression. The inductive mechanism for ILC2 plasticity was mapped to the IL-12/IL-12R signaling pathway and was confirmed through analysis of patients with Mendelian susceptibility to mycobacterial disease (MSMD) due to IL-12R?1 deficiencies that failed to generate plastic ILC2. This IL-13+IFN-?+ ILC2 are detected ex vivo in gut tissues from CrohnÕs patients. Second, I identified and isolated ILC precursors (ILCP) in peripheral blood of healthy donors. This circulating ILCP can give rise to four lineages of mature ILC including cytotoxic NK cells and helper ILC1, 2 and 3 in vitro and in vivo. Transcirptomic and epigenetic analysis showed ILCP have ILC-committed transcription factor profiles but have mature ILC signature locus at the epigenetics poised states. We further identified ILCP in various tissues including fetal liver, cord blood, postnatal lung and tonsil. Our result proposed a new model of ÒILC-poiesisÓ where circulating ILCP serve as cellular substrates to generate mature ILC subsets in tissues. Understanding the role of IL-12 on driving ILC2 to ILC1 plasticity may allow us to target plastic ILC2 in various diseases. The identification and isolation of ILCP from circulating blood allow further transfer into clinical setting for cellular therapy, especially for various diseases that ILC has been shown to be importance including infection, allergy, cancer and metabolic diseases
Jacomet, Florence. "Étude d'une nouvelle population de lymphocytes T « innate-memory » : implication dans l'immunité anti-leucémique au cours de la leucémie myéloïde chronique." Thesis, Poitiers, 2015. http://www.theses.fr/2015POIT1406/document.
Повний текст джерелаChronic myeloid leukemia (CML) is a myeloproliferative disorder that results from dysregulated tyrosine kinase activity of the fusion oncoprotein BCR-ABL, which is sufficient to induce malignant transformation. A critical role of the immune system in the control of CML is supported by several reports. Invariant Natural Killer T (iNKT) lymphocytes are a population of non-conventional T cells that are believed to play a key role in cancer immunosurveillance. Here, we showed that CML in chronic phase is associated with anergy of iNKT cells that is restored upon complete cytogenetic remission (CCyR) following Imatinib Mesylate (IM) or IFN-α therapy. In mouse, iNKT cells are involved in the generation of a recently characterized subset of innate CD8 T cells. Importantly, we provided definitive evidence of the existence of an equivalent of these innate CD8 T cells in humans, harboring innate and memory phenotype with high Eomesodermin expression. These cells also exhibited innate functions such as prompt IFN-γ expression in response to innate stimulation by interleukin (IL)-12 and IL-18 and cytolytic activity in a TCR independent manner.Size and functions of this innate-like CD8 T cell subset were severely impaired in CML patients at chronic phase. These defects were partially reversed in patients who achieved CCyR following IM treatment.Altogether, these results reveal a possible contribution of innate CD8 T lymphocytes in anti-leukemic immunity and should contribute to development of immunotherapeutic strategies against CML
Bergin, Stephen Michael. "Hypothalamic brain-derived neurotrophic factor regulates lymphocyte immunity, energy balance, and cancer progression." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487669797216355.
Повний текст джерелаRaffray, Loïc. "Immunopathologie de la leptospirose humaine : exploration de la réponse immunitaire innée." Thesis, La Réunion, 2017. http://www.theses.fr/2017LARE0006/document.
Повний текст джерелаLeptospirosis is a bacterial zoonosis caused by Leptospira and affecting 1 million people each year worldwide and mainly in tropical areas such as Reunion Island. Usual presentations encompass flu-like syndrome to multiorgan failure with mortality rate between 5 to 10%. To date, pathophysiology in humans is poorly understood, notably the capacity of innateimmunity to mount a robust response to clear pathogen or to induce tissue damages and contributing to disease severity. Our study aimed at assessing the role of innate immune cells and molecules within the first days of leptospiral infection.Using blood samples, we performed quantitative and qualitative assessment of circulating innate immune cells from leptospirosis cases and healthy controls. The first study explored the levels of gamma-delta T-cells (γδT-cells), a subset of unconventional T cells with innate immune functions. Gamma-delta T cells were found deeply decreased and levels wereinversely correlated to bacterial burden and liver damage. The second study focused on membrane bound receptors indicative of activation and tissue migration ability of neutrophil polymorphonuclear cells: CD15, CD11b, and CD182. Although neutrophil rates were high in leptospirosis cases, the levels of studied receptors were either lower (CD15) or identical to healthy controls (CD11b, CD182). In addition, only low levels of interleukin-8, a key chemokine for neutrophils, was detected in patients. Lastly, we ascertained the plasmatic levels of several shed cell adhesion molecules notably expressed by endothelial cells. The levels of soluble E-selectin and ICAM-1 were significantly increased compared to controls, while P-selectin level was lower. We did not find any correlation with disease severity or organ failure. This finding indicates that endothelial cell may be activated but further experiments are warranted to explain the functional impact of our findings. Altogether, our results add to the field of knowledge of leptospirosis pathophysiology, and in particular the implication of key innate immune cells at the stage of plasmatic bacterial dissemination. Our findings will support the view that there is an inappropriate immune response to Leptospira
Grimaldi, David. "Mécanismes cellulaires et moléculaires de l’immunodépression post-infectieuse." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05T049/document.
Повний текст джерелаSevere sepsis leads to a dysregulated inflammatory response followed by a complex immunosuppressive state that can favor the emergence of nosocomial infections. The cellular and molecular mechanisms that drive the post-infective immunosuppression remain poorly understood. They may involve immune cells that link innate and adaptive immunity such as dendritic cells or innate-like lymphocytes. Furthermore, Toll-like receptors (TLR) are critical determinants of the inflammatory response but their role to the development of sepsis-induced immune dysfunction are unknown. The aim of this research project was to investigate the role of dendritic cells, innatelike T cells and TLR-dependent signalling pathways in the sepsis-induced immunosuppression process. For this purpose, we combined a translational and experimental approach. We assessed dendritic cells blood count in septic patients and showed that the depletion of dendritic cells was associated with the advent of nosocomial infections. We studied 3 populations of innate-like T-cells (γδ lymphocytes, NKT- and MAIT-cells) in septic patients and demonstrated that only the MAIT-cells presented a significant depletion following severe sepsis, the persistence of which was correlated with the advent of nosocomial infection. Last, using knockout mice, we analyzed the relative contribution of TLR2, TLR4 and TLR5 to the host response in a model of late-onset secondary Pseudomonas aeruginosa pneumonia following a sublethal polymicrobial sepsis. We observed that TLR2 deficient mice were specifically protected against the secondary pneumonia through a better bacterial clearance. Our results provide new insights in the pathophysiology of post-infective immunosuppression and suggest potential therapeutic applications
Mozeleski, Brian Matthew. "The presence of an effector CD4 T cell population at birth." Paris 7, 2014. http://www.theses.fr/2014PA077009.
Повний текст джерелаThe immune response in the newbom is characterized by limited protection (<6 mo), low Ab responses (<12-24 mo), and limited T cell responses characterized by a biased towards Th2 responses. Minimal IFN-D producing T cell— responses fail to defend against microbial infection contributing to the WHO estimation that 2M children between 1-6 mo die each year from preventable infections. Human T cell development begins at —10 gestational weeks (g. W. ) where cells then egress from the thymus to colonize the periphery. Around 20 g. W. , terminal deoxynucleotidyl transferase expression is initiated, conferring maximum TCR diversity. Pregnancy requires establishment of a feto¬maternai tolerance state between mother and fetal antigens at the fetal interface. Similarly, the fetus develops regulatory T cells to maternai antigens. Therefore at birth and in the absence of any fetal infection, the T cell compartment putatively contains only naïve and regulatory T cells. Here we characterized the newbom' s peripheral CD4+ T cell compartment in ternis of its maturity and its potential to develop or elicit a diversity of effector functions. CD127hi and CD12710 expression separates conventional CD4+ T cells from Tregs respectively. Apart from CD127hi T cells and CD127lowFoxp3 Tregs, we identified a small population of CD45RO+CD127hi cells devoid of Foxp3 expression in cord blood. These cells represent around 3% of the total CD4+ population and were consistently found in ail cord blond samples (n=10), in the absence of any reported natural infection of the fetus. Following anti-CD3 and anti-CD28 stimulation, and within hours these cells produced Thl and Th2 effector cytokines IFN-y, IL-13, and IL-4, but IL-22 and IL-17a remained undetected. The presence of adult Th subset associated chemokine receptors (CXCR3, CCR4, CCR6) in cord blond promoted the screening conventional putative Th subsets for cytokine response and showed that the 1FNy response could be isolated to CXCR3+ while IL-4 and IL-13 were produced on ail subsets expressing a Th subset associated CCR. Direct microarray analysis comparisons of putative cord blood Th subsets versus defmed adult Th subsets revealed distinct adult-like signatures as well as a degree of plasticity in sharing Th2-like functions such as IL-4 and IL-13 production. The striking evidence that a mature T cell compartment exists at birth raises the question of how conventional T memory develops and winch antigens stimulate a response. Overall, these T memory cells may also influence the development of T cell responses in early life and offer important insight for the design of new and future neonatal vaccines
Lopez-Lastra, Silvia. "Humanized Mice as Models to study Human Innate Immunity and Immunotherapies." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS039/document.
Повний текст джерелаAnimal models have extensively contributed to our understanding of human immunobiology and to uncover the underlying pathological mechanisms occurring in the development of the disease. However, mouse models do not always reproduce the genetic complexity inherent in human disease conditions. Human immune system (HIS) mouse models that are susceptible to human pathogens and can recapitulate human hematopoiesis provide one means to bridge the interspecies gap. Severely immunodeficient host mice support life-long, high level human hematolymphoid development after engraftment with human hematopoietic stem cells (HSC). However, the differentiation and function of some blood cell types, including innate lymphoid cells (ILCs), is poorly characterized in current HIS mice. Here we describe the development of a novel HIS mouse model, named BRGSF, which demonstrate enhanced maturation, function and homeostasis of human natural killer (NK) cells and other ILCs. Furthermore, the BRGSF-based HIS mouse model recapitulated the developmental stages of human ILCs. We could identify for the first time an ILC precursor (ILCP) population that is present both in HIS mice and in human peripheral blood as well as in several lymphoid and non-lymphoid human tissues. This circulating human ILCP population may provide a substrate to generate mature ILCs in tissues in response to environmental stressors, inflammation and infection. In a second part of the thesis we used BRGS immunodeficient mice to assess two innate lymphocyte-based immunotherapeutic approaches for treating EGFR-expressing KRAS-mutated colorectal carcinoma in vivo. The first model used a combination of umbilical cord blood (UCB)-derived NK cells and the monoclonal antibody cetuximab to promote antibody dependent cell cytotoxicity (ADCC) against the tumors. In a second model, we evaluated the therapeutic suitability of novel bispecific VHH constructs that combine inhibition of the EGFR with the target-specific activation of effector Vγ9Vδ2-T cells. These studies highlight the utility for HIS-based mouse models to understand human innate lymphocyte development and to harness these potent effectors for anti-tumor therapies
Romo, Saladrigas Neus. "Innate response to human cytomegalovirus and the role of infections in the pathogenesis of atherosclerosis." Doctoral thesis, Universitat Pompeu Fabra, 2011. http://hdl.handle.net/10803/78874.
Повний текст джерелаHem analitzat la resposta de la cèl•lula NK als macròfags proinflamatoris (M1) i antiinflamatoris (M2) derivats de monòcits autòlegs infectats pel citomegalovirus humà (HCMV). Els macròfags M1 son més reistents a la infecció i secreten TNF-[alfa], IL-6, IL-12 i IFN de tipus I. Per altra banda, en els macròfags M2 infectats per HCMV la producció de citoquines proinflamatories, IFN de tipus I i IL-10 es limitada i la IL-12 indetectable. La cèl•lula NK degranula al interaccionar amb els macròfags M1 i M2 infectats. Aquesta degranulació s’inhibeix parcialment al bloquejar amb anticossos específics anti-NKp46, anti-DNAM-1 i anti-2B4, això indica que aquests receptors tenen un rol important en el procés. En canvi, només els macròfags M1 infectats amb HCMV promouen de manera eficient la producció d’IFN-[gamma] per part de la cèl•lula NK, degut parcialment a la producció de IL-12. Aquestes observacions posen de manifest diferències en la resposta de la cèl•lula NK a diferents tipus de macròfags infectats per HCMV que pot ser relevant en la patogènesis d’aquesta infecció viral. S’ha proposat que la infecció per HCMV contribueix al desenvolupament de l’aterosclerosis, un procés inflamatori crònic en el que els macròfags tenen un paper clau. La contribució del HCMV a la malaltia cardiovascular pot dependre de la resposta immune. La infecció per HCMV en donants de sang sans s’ha associat a canvis en la distribució dels receptors de les cèl•lules NK. S’ha evaluat la possible relació entre la infecció per HCMV, la distribució dels receptors de les cèl•lules NK i l’infart agut de miocardi. S’ha observat una associació de l’infart agut de miocardi i l’aterosclerosi subclínica tant amb les cèl•lules NK LILRB1+ com amb les cèl•lules T LILRB1+. Això possiblement reflexa la relació entre la pressió que les infeccions exerceixen en el sistema immunitari i el risc cardiovascular sense atribuir un paper principal al HCMV.
Gérart, Stéphane. "Identification d’un nouveau mécanisme de contrôle de l’homéostasie des lymphocytes T iNKT et MAIT." Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05TO22/document.
Повний текст джерелаInvariant natural killer T (iNKT) lymphocytes represent a peculiar T cell-lineage that differs from conventional T cells by its development, function, and ligands it recognizes. In humans, iNKT cells express an invariant TCR made of the V?24-J?18/V?11 rearrangement, which recognizes glycosphingolipids presented by the MHC class I monomorphic molecule CD1d. Moreover, they rapidly produce high amounts of cytokines when stimulated and are thus considered as innate-like T cells. The molecular mechanisms that control the homeostasis of iNKT are poorly understood. XIAP (X-linked Inhibitor of Apoptosis) is a physiological inhibitor of caspases 3, 7 and 9 and is mutated in the X-linked lymphoproliferation syndrome 2 (XLP-2), a rare primary immunodeficiency (PID) characterized by a peculiar susceptibility to Epstein-Barr virus (EBV) infection. Patients with a XIAP deficiency exhibit a strong reduction of their iNKT cells in blood. Here, I report that XIAP is required for the survival of iNKT cells in humans. The requirement of XIAP correlates with a pro-apoptotic phenotype of iNKT cells that is not observed in conventional T cells. The increased susceptibility to apoptosis of iNKT cells was observed upon stimuli that trigger either extrinsic or intrinsic apoptosis pathways. iNKT cells by contrast to conventional T cells express elevated amounts of pro-apoptotic molecules including caspases 3 or 7 and Bid. The pro-apoptotic phenotype of iNKT cells is early acquired since iNKT cells from cord blood and thymus display a similar pro-apoptotic phenotype. Knock-down of XIAP in iNKT cells and analysis of XIAP-deficient humans indicate that XIAP is a potent inhibitor of apoptosis in iNKT cells while it has only a moderate effect in conventional T cells. I also show that this pro-apoptotic phenotype of iNKT cells is dependent of the expression of the transcription factor PLZF. This factor is already known to be necessary for the acquisition of the effector functions of these cells. Conversely, over expression of PLZF in conventional T cells leads to a pro-apoptotic phenotype and to an increased expression of caspase 3. Recently, a second invariant T cell subpopulation, the mucosal associated invariant T (MAIT) cells was identified both in humans and mice. These cells express a semi-invariant TCR made of V?7.2-J?33 rearrangements and share with iNKT cells a number of developmental, functional and phenotypical features that lead to consider MAIT cells as innate-like T cells like iNKT cells. Similarly, MAIT cells also exhibit a pro-apoptotic phenotype and are decreased in XIAP-deficient humans. The pro-apoptotic phenotype of MAIT cells is also dependent on PLZF. Interestingly, one XIAP-deficient patient with normal iNKT cell number was identified. This patient has not yet encountered EBV, suggesting that reduction of iNKT cells in XIAP-deficient patients is likely due to increased apoptosis in the context of EBV infection. I also show that EBV might have an escape mechanism from iNKT cells by down-regulating the expression of CD1d on the surface of B cells. My thesis works identify a previously unknown pathway controlling innate T cell homeostasis depending on XIAP and PLZF. PLZF is thus a key factor involved in the differentiation and the homeostasis of innate T cells by regulating the acquisition of their effector functions and their survival. I also identified the first PID associated with a defect in MAIT cells. Finally, these results provide evidences that iNKT cells might play a role against EBV infection
Tout, Issam. "Rôle du TLR9 et des lymphocytes B dans l'échappement du virus de l'hépatite B à l'immunité innée." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1308/document.
Повний текст джерелаChronic HBV infection is a major health problem worldwide. Ineffective T cell and antibody responses have been demonstrated, yet the precise events that may contribute to insufficient B cell responses remain to be determined. Optimal B cell function, expansion and differentiation rely on Toll Like Receptor 9 (TLR9) activity which senses dsDNA and is expressed in human mainly by plasmacytoid dendritic ( pDC) and B cells. The impact of HBV on TLR9 in human B cell subsets remains to be explored.Here, we investigated the effects of HBV on TLR9 function in human B cells. Both primary and B cell lines were used to analyze the effect of HBV on TLR9 expression and function. These results were corroborated in a cohort of chronically infected HBV patients. TLR9 expression was reduced in all peripheral blood B cells subsets exposed to HBV. B cell function mediated by TLR9, such as proliferation and pro-inflammatory cytokines secretion were abrogated in the presence of HBV. Our results show that the viral surface antigen HBsAg inhibited the phosphorylation of the transcription factor CREB which could no longer bind the CRE site located on the TLR9 promoter. Finally, we corroborated our in vitro findings in a cohort of chronic HBV carriers (CHB) and found that TLR9 expression and function were significantly suppressed.Our findings reveal the mechanism that induces an immunosuppressive response by HBV on TLR9 function in human B cells, which may contribute to HBV persistence in the host
Patrick, Christopher. "Cereal Induced Autoimmune Diabetes is Associated with Small Intestinal Inflammation, Downregulated Anti-Inflammatory Innate Immunity and Impaired Pancreatic Homeostasis." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/30391.
Повний текст джерелаDaniel, Lauren. "Les lymphocytes T CD8 innés, une nouvelle population T non conventionnelle (re)programmée en transplantation rénale." Thesis, Poitiers, 2021. http://www.theses.fr/2021POIT1403.
Повний текст джерелаInnate CD8 T-cells are a non-conventional αβ-T-cell population recently described in our laboratory. We call them “non-conventional” because of their expression of markers from both adaptive immunity (transcription factor Eomesodermin and memory T-cell phenotype) and innate immunity (Natural Killer cell receptors, response to innate-like cytokine stimulation). The functions of innate CD8 T-cells are not well-known, although there are strong arguments for their involvement in anti-infectious and anti-tumor immunity.It has been reported that immunosenescence and/or chronic antigenic stimulation (induced, for example, by chronic viral cytomegalovirus (CMV) infections) result(s) in NK marker expression by T-cells. This phenotype is therefore similar to that of our cells of interest. To study the influence of chronic antigen stimulation on CD8 T-cells, and especially their innate component, we chose organ transplantation as a model. In this domain, research has been focused on immune cell populations that may play a role in graft tolerance or rejection. Among them, innate CD8 T-cells deserve special attention due to their effector/cytotoxic innate functions. We presumed their being reprogrammed by graft and/or viral chronic stimulation during organ transplantation. This hypothesis was tested in a cohort of patients with kidney-transplants for more than ten years, under minimized immunosuppressive treatment (ciclosporin A (CsA) monotherapy), without any clinical and biological sign of rejection. First, our work revealed a more accentuated senescent phenotype (increased frequency of CD27(-)CD28(-) cells) in innate CD8 T-cells from healthy donors (HD) than in their conventional counterpart. Moreover, the frequency of the innate T-cell population, unlike that of conventional CD8 T-cells, did not correlate with age.In the cohort of transplant patients, we observed an increased frequency of innate CD8 T-cells, accompanied by an exacerbated senescent and terminal effector (CD45RA(+)CCR7(-)) phenotype, compared to HD cells. Patients with positive CMV serology had an increased senescent phenotype compared to patients with negative serology.By altering TCR signaling, CsA immunosuppressive therapy could also facilitate the (re)programming of CD8 T-cells in favor of their innate counterpart. In agreement with this hypothesis, in vitro modeling of CsA effects on CD8 T-cells from HD in the presence of IL-15 and TCR stimulation enabled us to document an increased innate CD8 T-cell pool to the detriment of the naive CD8 T-cell pool, accompanied by an enhancement of their functions (innate production of IFN-γ).Conversely, in transplant patients, innate CD8 T-cells were dysfunctional, with decreased innate IFN-γ production, which may result from their decreased membrane expression of the IL-15 receptor, a cytokine essential for innate CD8 T-cells. This dysfunction, which cannot be attributed to cellular exhaustion or cancer history, raises the question of the role of chronic allo-specific stimulation.All in all, this work suggests that the context of renal allogenic transplantation leads to reprogramming and aging-like phenotype of innate CD8 T-cells, linked (at least partially) to immunosuppressive treatment. This hypothesis requires confirmation by a precise analysis of the direct allo-specificity of innate CD8 T-cells against the graft
Ebbo, Mikaël. "Rôle des cellules lymphoïdes innées chez l'homme : analyse au cours de déficits immunitaires, pathologies auto-immunes et inflammatoires." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0398.
Повний текст джерелаInnate lymphoid cells (ILCs) are recently identified components of the immune system, but their functions in vivo in humans are still elusive. In a first study, we show in patients with common variable immunodeficiency that non-infectious inflammatory complications and severe bacterial infections were more frequent in patients with severe NK cell lymphopenia, indicating potential non-redundant immune functions of NK cells when the adaptive immune response is not optimal. In a second study, we observe that in patients with ɣc and JAK3 severe combined immunodeficiencies, all ILC subsets are absent. After hematopoietic stem cell transplantation, ILCs remain indetectable with no susceptibility to disease, suggesting that ILCs might be redundant and dispensable in humans, if T and B cells functions are preserved. In the second part of this thesis, we study phenotypic and functional modifications of NK cell compartment in primary immune thrombocytopenia. Interferon gamma production by the peripheral blood NK cells of ITP patients is decreased. In contrast, splenic NK cells of ITP patients tend to be more efficient in antibody-dependent cell cytotoxicity. Intravenous polyvalent immunoglobulins lead to the inhibition of blood NK cell activation. Finally, we present the preliminary results of a study investigating the modifications of circulating ILCs in IgG4-related disease, and present an extensive litterature review concerning the role of ILCs in inflammatory diseases. In conclusion, the apparent redundancy of ILCs for protective immunity and their pathogenic role in inflammatory diseases make their targeting in humans for therapeutic purposes particularly promising
Silverstein, Noah J. "Disease Tolerance, Epigenetic Inheritance, and Surviving Pathogenic Viral Infections." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1149.
Повний текст джерелаDe, Wilde Virginie. "Dialogue entre l'immunité innée et acquise en réponse au lipopolysaccharide." Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210371.
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Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
Mahay, Guillaume. "Etude de l'initiation de la tolérance de l'immunothérapie spécifique aux venins d'hyménoptères par ultra-rush Ultra-rush venom immunomotherapy induces basophils inhibition by a lower surface expression of FcεRI and leads to early change in innate and adaptive immune response". Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR091.
Повний текст джерелаHymenoptera venom immunotherapy (VIT) is a treatment that prevents sting inducing anaphylaxis in allergic patient. Fast-up dosing schedule are often used at the initial phase of VIT. This fast dosing schedule well tolerated, but the mechanisms behind this good tolerance have not yet been elucidated, as well as its consequences on the rest of the immune systems. The aim of this study is to describe early immune system change during initial phase of VIT We included 29 patients undergoing VIT by 3h30 ultra-rush up dosing phase. Blood puncture was performed before the beginning of the treatment, at 1h30 and just before the last venom injection. Blood tryptase evolution was measured. Basophils phenotype and FcεRI surface expression were analyzed by flow cytometry at each step of the ultra-rush. To assess basophils responsiveness evolution, basophils activation test (BAT) was also perform. Myeloid and T lymphocytes population’s evolution were analyzed by flow cytometry. We have shown a significantly lower concentration of blood tryptase at the end of ultra-rush, and a significantly lower basophils activation and FcεRI expression. Surprisingly, BAT has shown a significantly higher in vitro response to venom extract at the end of ultra-rush. We also found significantly increase in blood dendritic cells concentration and lower blood Natural Killer (NK) Cells. We observed higher lymphocytes population in blood except for naïve CD4+ and CD8+ T cells. In conclusion, ultra-rush fast up dosing is well tolerated thanks to a basophils inhibition involving lower FcεRI surface expression. Ultra-rush also leads to early change in innate and adaptive immune response
Sanchez, Carole. "Analyse des sous populations lymphocytaires, et plus particulièrement les cellules NK, dans la polyglobulie primitive." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM5059/document.
Повний текст джерелаCharacterized by the presence of the JAK2 V617F mutation, polycythemia vera's development is content by phlebotomy but is associated with a higher incidence of cancer. A global exploration of the immunity of patients was performed by quantification of lymphocyte subpopulations of innate and adaptive immunity. This allowed the detection of a decrease in B cells and an increase in NK cells. NK cells are known for their antitumor properties but they are not yet able to eradicate PV, raising the question of their functional abilities. If NK cells of patients have a lower basal cytotoxic activity than healthy donors, they do not show abnormal expression of their receptors, the production of cytolytic molecules or proliferation. On the contrary, NK cells from a patient who developed erythroleukemia or NK cells from elderly healthy donors compared with younger healthy donors exhibit abnormalities of receptors expression. The increase in NK cells could be related to the JAK2 V617F mutation. If the mutation is present in cells of all patients, there are arguments for its presence in the NK cells of some patients. Finally, transcriptome analysis has identified an expression profile specific to NK cells of patients
Prokopová, Tereza. "In vitro test buněčné imunitní odpovědi pro diagnostiku Lymeské boreliózy." Master's thesis, 2017. http://www.nusl.cz/ntk/nusl-367822.
Повний текст джерелаBrandt, Philip. "Expression von Lymphotaktin (XCL1) bei der Wegener'schen Granulomatose." Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-0006-B320-8.
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