Dissertations / Theses on the topic 'Antigen Presenting Cell'
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Chang, Nan-Hua. "Selective elimination of antigen-specific T cells by antigen-targeted drug-labeled antigen-presenting cell membranes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ27889.pdf.
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Hudson, Sarah. "Myeloid antigen presenting cell populations in the murine uterus /." Title page, abstract and contents only, 2000. http://web4.library.adelaide.edu.au/theses/09PH/09phh887.pdf.
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Fidler, Sarah. "Antigen presenting cell function in HIV-1 infection." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300156.
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Dorrell, Lucy. "Antigen-presenting cell function in HIV infection and tuberculosis." Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241984.
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Wyss-Coray, Anton. "The human T lymphocyte as an antigen presenting cell /." [S.l : s.n.], 1993. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Bergamin, Fabio. "Antigen-presenting cells and BAFF in porcine B-cell responses against FMDV /." Bern : [s.n.], 2007. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Pecora, Nicole Danielle. "TLR₂-dependent modulation of antigen presenting cell functions by mycobacterial lipoproteins." Cleveland, Ohio : Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1212611434.
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Giusti, Pablo. "Characterization of antigen-presenting cell function in vitro and ex vivo." Doctoral thesis, Stockholms universitet, Wenner-Grens institut, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-60433.
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Long-term protective immunity depends on proper initiation of professional antigen-presenting cells (APCs). Autoimmune disorders and certain infections can cause disease through modulation of APCs and thereby affecting the outcome of these diseases. This work aimed to investigate the behaviour of different APC subsets during conditions known to cause improper immune responses. In Paper I, the effects of an anti-inflammatory compound called Rabeximod, intended for treatment of rheumatoid arthritis were investigated on different subsets of APCs. The results showed that Rabeximod affected the differentiation and behaviour of inflammatory subsets of dendritic cells (DCs) and macrophages while no effects were observed on anti-inflammatory subsets. Our findings suggest that Rabeximod acts by inhibiting the functionality of inflammatory subsets of APCs. In Paper II, the effects of different malaria derived stimuli such as hemozoin (Hz) and infected red-blood cells (iRBCs) on monocyte-derived dendritic cells (MoDCs) were investigated. Both stimuli triggered activation and migration of MoDCs. MoDCs exposed to iRBCs induced allogeneic T-cell proliferation while those exposed to Hz did not. These results indicate that different malaria derived stimuli may differently affect DCs and that this could lead to improper and inefficient T-cell activation. In Paper III, innate aspects of malarial immunity were compared in children from two sympatric ethnic groups. We observed decreased activation of APCs and severely supressed TLR responses in Dogon children as compared to Fulani. This may indicate an important role for TLR and APC activation in the Fulani, known to be better protected against malaria than the Dogon. In summary, detailed knowledge of APC activation will be helpful in the understanding of specific effector immune responses. This could in turn, improve treatment of inflammatory disorders as well as the generation of efficient vaccines against infectious diseases.
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Pecora, Nicole Danielle. "TLR2-Dependent Modulation of Antigen Presenting Cell Functions by Mycobacterial Lipoproteins." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1212611434.
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Mayer, Wolfgang. "The antigen presenting cell in the human cornea – functional and morphological evaluation." Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-143669.
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Markiewicz, Anna Maria. "Impact of syndecan-4 on T cell-antigen presenting cell recognition and the immunological synapse." Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/6987.
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Syndecan-4 (SDC-4), a transmembrane heparan sulphate proteoglycan and a co-receptor of integrins for fibronectin, has been reported to modulate the adhesion of cells to a range of extracellular matrix ligands. In addition to the modulation of integrins, SDC-4 has been recently reported to modify the interaction of some growth factors with their receptors. T cells are essential effectors of the adaptive immune response. When conjugating with antigen-presenting cells (APCs), T cells transform their shape to enable formation of a specialised morphological structure, called the immunological synapse (IS). The IS formation is associated with the polarisation of signalling and adhesive molecules towards the APC. The IS is formed and stabilized by similar adhesive forces and structures as in the motile fibroblasts - an extensively studied model of syndecan function. In this thesis I have investigated the role of SDC-4 in T cell - APC recognition and the IS. First, I confirmed the tight regulation of SDC-4 expression in T cells during the process of activation. Flow cytometry and PCR data demonstrate increased presence of SDC-4 in stimulated human T cells compared to their resting counterparts, indicating involvement of SDC-4 in the processes of T cell activation. Transient transfection of exogenous SDC-4 into Jurkat T cells with low endogenous SDC-4 expression was used as a model to study the effect of increased SDC-4 expression on T cell function. Using live cell imaging and advanced data image analysis I have quantitatively demonstrated that SDC-4 transfected Jurkat T cells are less likely to modify their shape during IS formation when compared to mock transfected Jurkat T cells. I also observed a delay in T cell antigenic response caused by SDC-4 over-expression. Moreover, I was able to visualise the exogenous SDC-4 in the IS using confocal microscopy and demonstrate the independence of this phenomenon on T cell receptor. In summary, my observations indicate a regulatory role for SDC-4 in T cell adhesion causing delays in the IS formation and reduced transformation of T cell shape during conjugate formation.
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Mohamed, Yehia Saleh Ahmed. "The use of antigen presenting cell/tumour cell hybrids for the in vitro induction of tumour-specific T cells." Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/10054.
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Malignant tumours are the second main cause of mortality worldwide, with haematological malignancies representing 10%. Current treatment strategies, such as chemotherapy, radiotherapy, and stem cell transplantation, are mostly effective but may induce serious side effects. In addition, tumours are developing resistance against most of these conventional therapies. Immunotherapy is a promising investigational approach, especially hybrid cell vaccination, in which a professional APC is fused to a tumour cell, and the fusion product mostly combines the antigenicity of the tumour cell partner, processed and presented through the relevant APC-machinery, and associated with co-stimulatory molecules CD80, CD86, and CD40 expression, for proper induction of anti-tumour immune responses. I investigated the phenotypic and functional characteristics of a group of previously-made hybrid cell lines, generated by in vitro fusion of a human APC (HMy2; EBV B-lymphoblastoid cell line) with haematological ex vivo or immortalized tumour cells. On co-culture with allogeneic (normal donors) peripheral blood lymphocytes, hybrid cell lines induced elevated levels of T-cell proliferation compared with their relevant tumour cells, which was dependent on expression of co-stimulatory molecules CD80 and CD86, and MHC class I and class II antigens. The hybrid cell lines induced proliferation of naive, central memory, and effector memory populations of CD4+, CD8+ T-cells. Moreover, the hybrid cells expressed a range of tumour associated antigens not expressed by HMy2 cells, or by normal PBMC. Depending on that, tumour-specific cytotoxic T lymphocytes were induced in vitro by stimulation of allogeneic or autologous PBMCs for multiple rounds with selected hybrid cell lines in the presence of rhIL-2. Tumour- and antigen-specificity of the activated T cells were assessed by IFN-γ releasing ELISpot, MHC class I (HLA-A2)-restricted tumour peptide-specific pentamer staining, and 51Cr-release cytotoxicity assays. Hybrid cell vaccines generated in this way may therefore represent a novel strategy for use in immunotherapy of haematological malignancies, and possibly in other forms of cancer as well.
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Hutchings, Anne. "Antigen presenting cells and transplantation : a comparison of immune cell function between Caucasians and African Americans." Thesis, University of the West of England, Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365190.
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Doty, Raymond Thomas. "The role of the cytoplasmic tail of antigen-presenting cell surface molecule CD80 in delivery of T cell costimulation /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/8327.
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Zhang, Jingnan [Verfasser]. "Engineered antigen-presenting hydrogels : model platforms for studies of T cell mechanotransduction / Jingnan Zhang." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2020. http://d-nb.info/1214640850/34.
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Reuter, Morgan Ann. "Mycobacterium tuberculosis-induced changes in HIV-1 trafficking in human antigen presenting cells." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1278699683.
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De, la Pena H. "Development of a novel nanotechnology based artificial antigen presenting cell system for adoptive and active immunotherapy." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1446304/.
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T cells are one of the most pivotal cell types in the human adaptive immune system. They have the capacity to eradicate primary, metastatic, relapsed tumours and can ameliorate otherwise fatal viral infections. Not surprisingly therefore, the activation and expansion of T cells has become one of the main focuses for immunotherapy and immune gene therapy. However one of the problems of T cell mediated immunotherapy in terms of delivering significant clinical impact to patients, is the expansion of high numbers of functional antigen specific effector T cells. The current approaches for expanding T cells have a number of drawbacks in terms of timing, reproducibility and reliability. Many if not all the currently available systems rely on ex vivo cell manipulation, which concordantly leads to short T cell survival in vivo after infusion. In vivo artificial expansion systems would clearly circumvent this problem. Nevertheless active immunotherapy is not always the solution since sometimes in some patients, the T cells that could be potentially in- vivo expanded no longer exist because they have been deleted, killed or anergised. Therefore a flexible system should be constructed in order to performed both adoptive and/or active immunotherapy depending on the patients requirements. Currently there is no comprehensive artificial Antigen Presenting Cell system (aAPC) for both effective ex vivo and in vivo antigen specific T cell expansion. Therefore in order to address this we have constructed a novel artificial nano-sized super para magnetic antigen presenting cell system (aAPC) capable of priming and expanding antigen specific T cells ex vivo and in vivo. As defined by the NIH, nanotechnology uses nanoscale injectable, targeted and traceable devices capable of important immunological/clinical functions. This nano-system was constructed using the latest generation of immuno liposomes, approved for in vivo human use since they are non-toxic, biodegradable, avoid rapid recognition by the reticulo endothelial system, are safe in terms of size being 50 times smaller than average cells at lOOnm, have good stability and favourable pharmacokinetic behaviour for effective in vivo trafficking. We have coated these liposomes with an optimised number of MHC Class I / peptide complexes and a specific selected range of adhesion (anti LFA-1), early activation (anti CD28 and anti CD27), late activation (4-IBB) and survival receptors (anti CD40L) in the form of Fab antibody regions or monoclonal antibodies. We have made these immuno liposomes traceable since they carry fluorescent lipids and iron oxide super para magnetic nano particles or spios of 13nm size, which make them traceable in vivo using fluorescence and/or by Magnetic Resonance Imaging (MRI). The super para magnetic liposomes are also able to facilitate their own focusing to specific organs, tumour sites or body areas by applying external magnetic attraction. Production of this nano immune liposome system in a ready to use form is achievable in less than 48 hrs and viable for at least 7 days. After ex vivo stimulation with this artificial nano system using CMV pp65 as a model antigen, we have established successful expansions with high T cell numbers (55 to 200 fold) in CMV positive individuals, which are superior when compared with other systems such as peptide pulsed DCs, which are one of the standard methods currently used, coated Daudi cells, magnetic commercial beads and modified tetramers. The T cells are fully functional in terms of degranulation and production of cytokines when specifically challenged. They express predominantly effector-memory and memory phenotypes. We have demonstrated by double fluorescent staining that these liposomes activate T cells directly in an antigen specific fashion and also semi-directly by being incorporated on the surface of the natural APCs in a similar manner as exosomes. When tested in naive individuals, this nano system was also capable of accomplishing initial low levels of T cell priming without help of any adjuvants. In conclusion, we have generated an efficient artificial APC, which embodies a powerful, controllable and superior approach with enormous potential for cancer nanotechnology and T cell immunotherapy for use either in vivo or in vitro.
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Mayer, Wolfgang J. [Verfasser], and Daniel [Akademischer Betreuer] Kook. "The antigen presenting cell in the human cornea – functional and morphological evaluation / Wolfgang Mayer. Betreuer: Daniel Kook." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2012. http://d-nb.info/1023206048/34.
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Liao, Wenqing. "Development of Nanostructured DNA Aimed at Enhancing the Stability and Antigen-presenting Cell Targetability of CpG Oligodeoxynucleotide." Doctoral thesis, Kyoto University, 2020. http://hdl.handle.net/2433/253234.
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京都大学0048
新制・課程博士
博士(薬科学)
甲第22398号
薬科博第120号
新制||薬科||13(附属図書館)
京都大学大学院薬学研究科薬科学専攻
(主査)教授 髙倉 喜信, 教授 山下 富義, 教授 小野 正博
学位規則第4条第1項該当
Doctor of Pharmaceutical Sciences
Kyoto University
DFAM
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Clark, Anel. "Development and validation of an in vitro model of dendritic cell identification and activation." Thesis, Stellenbosch : Stellenbosch University, 2008. http://hdl.handle.net/10019.1/21605.
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Thesis (MScMed)--Stellenbosch University, 2008.ENGLISH ABSTRACT: The aim of this study was to investigate the effect of MBV and Coley’s Toxin on dendritic cells in vitro. The dendritic cell system of antigen presenting cells is the initiator and modulator of the immune response. The principle function of the dendritic cells is to present antigens to resting naïve T lymphocytes: these cells are the only APCs that prime naïve T cells and only mature DCs can carry out this function.Previous studies done on dendritic cells showed that bacterial peptides can induce the maturation of dendritic cells. With the results of these studies in mind we hypothesized that these two vaccines will also induce the maturation of dendritic cells. Chapter 1 is a literature review on the immune system explaining the organs and cells of the immune system. Chapter 2 includes a full description of DCs, the MBV and Coley’s toxin. Also included in this chapter is a short explanation of the principle of the technique being used for the identification and maturation of both mDCs and pDCs, namely the technique of flow cytometry. Chapter 3 describes the method for the phenotypic identification of DCs: the subsets are distinguished by their absence of expression of several lineage markers for lymphocytes, monocytes and NK cells and the expression of CD11c (in the case of myeloid DCs) and CD123 (in the case of plasmacytoid DCs). The inclusion of HLA-DR in addition to the previous described markers allows the discrimination of CD123+ DCs from basophils. The assay requires three tubes per sample which enables quick analysis of these rare subsets with a small sample volume. This assay was applied to peripheral blood samples obtained from healthy individuals and individuals with cancer, HIV and HIV and TB co-infected patients. Our results showed that the maturation status of DCs in HIV and lymphoma were low but those measured in the case of HIV + TB patients were even higher than in the control group. Chapter 4 and 5 describe the in vitro activation and maturation status of DCs following their incubation with bacterial-derived products. Interactions between DCs and microbial pathogens are fundamental to the generation of innate and adaptive immune responses and upon contact with bacteria or bacterial components such as lipopolysaccharide (LPS), immature DCs undergo a maturation process that involves expression of costimulatory molecules, HLA molecules, and cytokines and chemokines, thus providing critical signals for lymphocyte development and differentiation. In this study, we investigated the response of human DCs to MBV and Coley’s Toxin. Previous studies showed DCs can be activated with killed Streptococcus pyogenes. With this study in mind it was hypothesized that the MBV and Coley’s Toxin used in this study might modulate DC maturation. The results of this study showed that the MBV and Coley’s toxin did induce the maturation of both pDCs and mDCs as measured by increased surface expression of costimulatory molecules such as CD80 and CD83. Chapter 6 presents the measurement of cytokines released after the PMBCs had been were incubated with Coley’s Toxin and Mixed Killed bacteria. The BD™ Cytometric Bead Array (CBA) flex set was used for the simultaneous detection of multiple soluble analytes. The results indicated that both Coley’s Toxin and the MBV activated the DCs and subsequently induced TH1 as well as a TH2 responses in the T cells present in the cell cultures. Finally, a general conclusion discussing the significance and implications of our results as well as possible future research required is discussed in Chapter 7. DCs are potent antigen presenting cells (APCs) which play a critical role in the regulation of the immune response. There is great interest in exploiting DCs to develop immunotherapies for cancer, chronic infections, immunodeficiency diseases and autoimmune diseases.
AFRIKAANSE OPSOMMING: Die doel van die studie was om die effek van ‘n gemengde bakteriële vaksiene en Coley se toksiene op dendritiese selle te toets in vitro. Die dendritiese sel sisteem speel ‘n belangrike rol in die modulering en reaksie van die immuun sisteem.Die hoof funksie van dendritiese selle is om antigene bloot te stel aan naïewe ongeaktiveerde T selle. Slegs volwasse dendritiese selle kan die T selle aktiveer. Vorige studies het bewys dat bakteriële peptiedes die veroudering van die dendritiese selle kan induseer. Met die resultate in gedagte het ons gehipotiseer dat die twee vaksienes ook die maturasie van dendritiese selle kan induseer. Hoofstuk 1 is ‘n literatuur studie wat handel oor die organe en selle van die immuun sisteem. Hoofstuk 2 gee n volle beskrywing van dendritiese selle, die gemengde bakteriële vaksiene en Coley se toksiene. Ingesluit in die hoofstuk is die beskrywing van die prinsiep van die tegniek, vloei sitometrie, wat gebruik word vir die identifikasie en veroudering status van die dendritiese selle. Hoofstuk 3 beskryf ‘n vloei sitometrie metode vir die fenotipiese identifikasie van dendritiese selle. Dendritiese sel tipes kan onderskei word deur die afwesigheid van sekere merkers vir limfosiete, monosiete en NK selle. Plasmasitoïede dendritiese selle druk CD123 uit en miloïede dendritiese selle druk CD11c uit. HLA DR is ook ingesluit saam met die bogenoemde merkers om die dendritiese selle te onderskei van basofiele. Vir elke toets word slegs drie buise geprosesseer en dus kan die subklasse vinning geanaliseer word. ʼn Klein volume bloed word benodig vir die toests. Perifêre bloed is gebruik vir die toets op bloed monsters van 10 gesonde individue en individue met kanker, HIV en HIV en TB. Die resultate van die studie het getoon dat die maturasie status van die dendritiese selle in HIV en limfoom was, maar in die geval van HIV en TB pasïente was die maturasie status selfs hoër as die van die kontrole groep. Hoofstuk 4+5 beskryf die aktivering en maturasie status van die dendritiese selle na inkubasie met die bakteriële produkte. Interaksie tussen dendritiese selle en patogene speel ‘n belangrike rol in die aktivering van die immuunstelsel. Wanneer dendritiese selle in aanraking kom met bakterieë of bakteriële komponente, matureer die dendritiese sel wat lei tot the uitdrukking van stimulerings molekules, HLA molekules end die uitskeiding van sitokiene. Die uitdrukking van die molekules lei tot limfosiet ontwikkeling en differensiasie. In die studie het ons gekyk na die reaksie van menslike dendritiese selle in die teenwoordigheid van die gemende bakteriële vaksiene en Coley se toksiene. Vorige studies het bewys dendritiese selle word geaktiveer deur Streptococcus pyogenes. Met die resultate in gedagte het ons gehipotetiseer dat die gemengde bakteriële vaksiene en Coley se toksiene ook die maturasie van dendritiese selle kan induseer. Die resultate van die studie het bewys dat die gemengde bakteriële vaksiene en Coley se toksiene die veroudering van beide pDCs en mDCs induseer. Die uitdrukking van verouderings merkers CD80 en CD83 is gemeet. Hoofstuk 6 beskryf ‘n vloei sitometrie metode om die sitokiene te meet wat afgeskei word nadat selle geinkubeer het in die teenwoordigheid van Coley se toksiene en die gemengde bakteriële vaksiene.Die BDTM CBA Flex set metode het dit moontlik gemaak om meer as een sitokiene te meet in net een buis Die resultate het getoon dat albei die vaksienes ‘n TH1 en TH2 reaksie veroorsaak. Laastens volg‘n algemene afleiding waar ons kyk na die toepassing en implikasies van die resultate asook toekomstige navorsings moontlikhede,word bespreek in Hoofstuk 7 Dendritiese selle speel ‘n kritiese rol in die regulering van die immuun reaksie. Verdere studies kan nou gedoen word om dendritiese selle terapeuties toe te pas vir die behandeling van kanker, autoimmuniteit, immuun onderdrukkende siektes en kroniese siektes.
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Salvioni, Anna. "Major histocompatibility complex class I presentation and CD8 T cell responses during cerebral toxoplasmosis." Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30262.
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Les molécules du Complexe Majeur d'Histocompatibilité de classe I (CMH I) contrôlent la plasticité synaptique dans le système nerveux central (SNC) et plusieurs travaux expérimentaux suggèrent des interactions antigène-dépendantes entre des neurones infectés par des virus et les lymphocytes T CD8. Cependant, le rôle de la présentation des antigènes par le CMH I des neurones sur la physiopathologie de l'infection par Toxoplasma gondii (T. gondii) n'a pas encore été clarifié. Après la dissémination aigue sous forme de tachyzoites, T. gondii se convertit en bradyzoites, forme persistante dans les neurones du SNC. Chez les individus immunocompétents, la toxoplasmose latente est associée à des variations des fonctions cognitives ainsi qu'à des pathologies neuropsychiatriques. Les sujets dont le système immunitaire est dysfonctionnel peuvent développer une encéphalite létale causée par T. gondii, qui est caractérisée par une réplication du parasite, une infiltration massive et des agrégats leucocytaires et l'activation des cellules gliales. Les lymphocytes T (LT) CD8 et le CMH I sont des facteurs-clés contrôlant la résistance à l'encéphalite. Utiliser les LT CD8 pour éliminer les kystes chez des sujets à risque est une piste thérapeutique intéressante en raison de l'absence d'approches pharmacologiques ciblant les bradyzoites. A ce jour, les mécanismes et la pertinence fonctionnelle de la présentation des antigènes dérivés de T. gondii par les neurones restent à déterminer, ainsi que la contribution des différents stades parasitaires au contrôle de l'infection. L'utilisation de nouveaux parasites exprimant un antigène immunodominant uniquement au stade tachyzoite a permis de montrer que la reconnaissance par les LT CD8 d'antigènes issus des tachyzoites est suffisante pour une protection efficace contre l'encéphalite.[...]In the Central Nervous System (CNS), Major Histocompatibility Complex class I (MHC I) molecules regulate synaptic plasticity and evidence suggests antigen-specific interactions between virus-infected neurons and CD8 T cells. Yet, little is known about the impact of neuronal MHC I presentation on the pathophysiology of infection by the neurotropic Toxoplasma gondii (T. gondii) parasite. Following acute dissemination as tachyzoites, T. gondii converts into bradyzoites that persist inside cysts within neurons of the CNS. In immunocompetent hosts, latent toxoplasmosis is associated with cognitive changes and neuropsychiatric disorders. Hosts with sub-optimal immune responses may develop a lethal T. gondii Encephalitis (TE), characterized by parasite replication, granuloma-like structures with massive immune cell influx and glial cell activation. CD8 T cells and MHC I are key determinants of TE resistance. Harnessing CD8 T cells in at-risk individuals may turn helpful in the future as we are currently lacking an effective pharmacological approach to eradicate bradyzoites. Yet the mechanisms and functional relevance of neuronal MHC I presentation of T. gondii remain unexplored, as well as which stage of the parasite contributes to efficient control of the infection. Using new T. gondii parasites with restricted expression of the immunodominant antigen at the tachyzoite stage, this work showed that CD8 T cell recognition of tachyzoite antigens at early stages of brain invasion is enough to protect from TE. Interestingly, by comparing situations of toxoplasmosis with varying TE severity and by pioneering antigen presentation assays with T. gondii-infected primary neurons, we revealed that TE susceptibility may be underlied by sub-optimal MHC I presentation of tachyzoites antigens by neurons. At last, we describe a mouse model that allows conditional deletion of a MHC I allele that is essential for TE resistance (H-2Ld). [...]
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Hutton, Andrew J. "Characterisation of the human lung fibroblasts ability to act as an antigen presenting cell for T helper cells of the immune system." Thesis, University of Southampton, 2015. https://eprints.soton.ac.uk/416623/.
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T helper cells of the immune system are critical in mediating immune responses in the lung. Through the release of cytokines, T helper cells direct the wider immune response against a range of pathogens and are considered indispensible for effective immunity. T cell activation is governed by the interaction with antigen-presenting cells (APCs), which mediate antigen-specific T cell activation and thus control immune responses in areas such as the lung. While T helper cell activation by APCs such as dendritic cells is well established, the role of fibroblasts in T helper cell activation in the lung is poorly understood. Fibroblast antigen presentation was hypothesised to be a mechanism leading to activation of bacterial-specific lung T helper cells. Characterisation of T cell populations within the human distal lung was carried out. focusing upon examining the memory T cell populations. In addition, the cytokine production profile of T cells as a whole population and in response to specific lung bacterial antigen was examined. Distal lung T cells were primarily CD4 T helper cells of an effector memory phenotype. IFNγ producing, Th1-type cells were the most abundant effector subset present in all T cell populations examined, while initial responses to the common lung bacteria nontypeable haemophilus influenza were more heterogeneous. Human lung fibroblasts obtained from the distal lung were examined for expression of immune synapse molecules both ex vivo and in vitro using flow cytometry. The ability of lung fibroblasts to internalize environmental antigen was also investigated via flow cytometry and confocal microscopy. Using autologous lung fibroblasts and T helper cells, the ability of fibroblasts to present bacterial antigens non-typeable haemophilus influenza was examined. T helper activation was measured via the production of cytokines associated with the major T helper effector subsets. Lung fibroblasts expressed HLA-DR ex vivo, and were shown to upregulate HLA-DR and ICAM-1 by IFNγ treatment in vitro, but did not express CD80 or CD86. Fibroblasts were also able to internalize environmental antigen. Fibroblasts exposed to both IFNγ and a heat-killed form of non-typeable haemophilus influenza are shown to activate IFNγ and IL-17A producing T helper cells in an antigen dependent manner. This study demonstrates that lung fibroblasts are able to function as an inducible APC and activate proinflammatory T helper cells. This previously unknown relationship between fibroblast and T cell may represent a key mechanism in lung immune responses to bacterial populations.
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Cabbage, Sarah E. "Reversible regulatory T cell-mediated suppression of myelin basic protein-specific T cells /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/5034.
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Burchell, Jennifer Theresa. "The role of regulatory T cells and dendritic cells in allergen-induced airways hyperresponsiveness." University of Western Australia. School of Paediatrics and Child Health, 2008. http://theses.library.uwa.edu.au/adt-WU2009.0006.
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Airway hyperresponsiveness (AHR) is one of the primary features of allergic airways disease. Despite continuous allergen exposure atopic asthmatics do not develop progressively worsening AHR. The mechanism(s) that limit AHR are unknown. Two valid candidates are regulatory T cells (Treg) and antigen presenting cells (APC). Dendritic cells (DC) are the main APC within the airways. Presentation of allergens to T cells can result in the differentiation and expansion of different subsets of T cells including effector Treg cells. The precise role of Treg and DC in the attenuation of allergen-induced AHR remains unknown. The general aim of this thesis is to investigate mechanisms to limit AHR in a murine model of atopic asthma. Specific aims are to: 1. develop a murine model of allergen-induced attenuation of AHR, 2. determine the potential role of regulatory T cells (Treg) in allergen-induced AHR attenuation, and 3. determine the potential role of airway dendritic cells (DC) in allergen-induced AHR attenuation. Balb/c mice were sensitised with intraperitoneal Ovalbumin (OVA) in aluminium hydroxide and challenged with a single, 3-weeks or 6-weeks of OVA aerosols. Aerosols were 1% OVA in sterile saline delivered for 30 minutes for three days per week. Animals were sacrificed 24 hours after the final aerosol for measurements of lung function and Methacholine (MCh) responsiveness (low-frequency forced oscillation technique), collection of bronchoalveolar lavage fluid (BALF) and serum. '...' In contrast, 6-weeks of OVA challenges decreased Treg numbers back to control levels. Adoptive transfer of 1x106 Treg taken from DLN of 3-week challenged mice attenuated AHR in single-OVA recipients (p<0.05). Furthermore, in vivo depletion of Treg in 3-week OVA challenged mice restored AHR (p<0.05 compared with control). Similar proportions of CD4+ T cells became activated following both aerosol regimes, however total numbers of airway CD4+ T cells were decreased (p<0.05), and OVA-specific CD4+ T cell proliferation in DLN was reduced (p<0.05) after 3-weeks versus one OVA aerosol. Analysis of antigen handling by airway APC populations showed antigen uptake (OVA-647) and processing (DQ-OVA) by macrophages and airway DC subsets to be down-regulated (p<0.05) after 3-weeks of OVA aerosols. In addition, adoptive transfer of Treg into single-OVA recipients did not affect antigen handling by airway APC populations. These data suggest that Treg are responsible for allergen-induced attenuation of AHR in vivo in established airways disease. AHR attenuation was associated with an altered function of airway DC, resulting in reduced antigen capture and processing, leading to limited clonal expansion of antigen-specific CD4+ T cells with limited production of Th2 cytokines. Furthermore, Treg were not directly responsible for the down-regulation of allergen capture in the airways. In conclusion, knowledge of the role of Treg and DC in attenuation of AHR could potentially result in improved and more directed therapies for the attenuation of AHR in atopic asthmatics.
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Fu, Jianing. "Targeting T-bet for Prevention of Graft-Versus-Host Disease and Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation." Scholar Commons, 2015. http://scholarcommons.usf.edu/etd/5828.
Full textAbstract:
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapeutic option for many malignant diseases. However, the efficacy of allo-HSCT is limited by the occurrence of destructive graft-versus-host disease (GVHD). Since allogeneic T cells are the driving force in the development of GVHD, their activation, proliferation, and differentiation are key factors to understanding GVHD pathogenesis. On the other hand, antigen-presenting cells (APCs) are essential for allogeneic T-cell priming and the development of GVHD. The T-box transcription factor T-bet is a master regulator for IFN-γ production and Th1 differentiation. T-bet also regulates the functions of APCs including dendritic cells (DCs) and B cells. Therefore, we investigated the role of T-bet in T cell responses, as well as on APC functions, in acute GVHD (aGVHD) using murine models of allogenic bone marrow transplantation (allo-BMT).
In Chapter 2, we evaluated the roles of T-bet and IFN-γ in T-cell responses. T-bet-/- T cells induced significantly less GVHD compared with either wild-type (WT) or IFN-γ-/- counterparts in CD4-driven major histocompatibility complex (MHC)- or minor histocompatibility antigen (miHA)-mismatched models. We defined several T-bet-dependent but IFN-γ-independent molecules that may account for this distinct outcome. Further study indicates that T-bet also controls the optimal activity of Th17 cells to induce GVHD. Moreover, the compromised graft-versus-leukemia (GVL) effect of T-bet-/- T cells could be essentially reversed by IL-17 neutralization. Thus, targeting T-bet or regulating its downstream effectors independent of IFN-γ may be a promising strategy to control GVHD in the clinic.
In Chapter 3, we evaluated the role of T-bet on APCs and found that T-bet-/- recipients developed much milder GVHD than their WT counterparts in MHC-mismatched or CD4-depedent miHA-mismatched models. As the functional readout of APCs, allogeneic donor T cells, particular CD4 subpopulation, significantly reduced IFN-γ production, proliferation and migration, and caused less damage in liver and gut in T-bet-/- recipients. We further observed that T-bet on recipient hematopoietic APCs, particular DCs, was primarily responsible for donor T-cell response and pathogenicity in GVHD. In fact, Trail/DR5 interaction served as a major signaling pathway responsible for donor T-cell apoptosis and impaired GVHD development in T-bet-/- recipients. Furthermore, T-bet expression on the host is largely dispensable for the GVL effect.
Taken together, we propose that T-bet is a potential therapeutic target for the control of GVHD through regulating T cells as well as APCs. We believe further exploration and understanding of the immunobiology of T-bet in controlling the activities of T cells and APCs in GVHD will expand therapeutic options for the continuing success of allo-HSCT.
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Sebastian, Katrin [Verfasser]. "Sensibilization of dendritic cell-like antigen-presenting cells by low-molecular weight drugs : molecular characterization and function of the dendritic cell-specific organic anion transporting polypeptide OATP5A1 / Katrin Sebastian." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2013. http://d-nb.info/1033988634/34.
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COLUCCI, MANUELA. "Immunomodulatory properties of cholera toxin B subunit." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/1019.
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L'immunità innata antigene-non-specifica e l'immunità adattativa antigene-specifica collaborano per debellare i patogeni che invadono l'organismo tramite l'intervento delle cellule del sistema immunitario e delle loro molecole effettrici, che includono le proteine del complemento, gli anticorpi, le citochine e i fattori deputati alla lisi cellulare. Le risposte immunitarie adattative vengono indotte, coordinate e regolate dalle cellule dendritiche (DC). Le DC avviano le risposte immunitarie attivando i linfociti B e T naïve – che sono le cellule effettrici dell'immunità adattativa – e stimolando le cellule natural killer, che sono le principali cellule effettrici dell'immunità innata. Accanto al loro ruolo di collegamento tra immunità innata e adattativa, le DC hanno il delicato compito di limitare le risposte infiammatorie eccessive, che potrebbero causare danni tissutali, con lo scopo di prevenire l'insorgenza di reazioni indesiderate contro antigeni autologhi o innocui. A questo scopo, le DC inducono nei linfociti uno stato di “non-responsività” contro gli antigeni sia negli organi linfoidi primari che in quelli secondari, attraverso meccanismi che includono la delezione e l'induzione di cellule T regolatorie (Tregs). Dal momento che presentano questo ruolo centrale sia nell'immunità che nella tolleranza, le DC dimostrano di essere un candidato ideale come bersaglio di farmaci immunomodulanti.
Nel presente studio abbiamo esaminato la possibilità che la CTB ricombinante (rCTB) possa influenzare le funzioni delle DC in risposta alla stimolazione tramite toll-like receptors (TLR), rendendo le DC capaci di indurre il differenziamento di Tregs.
La CTB – la subunità B della tossina colerica – è un'efficace proteina trasportatrice a livello mucosale, in quanto facilita l'internalizzazione degli antigeni ad essa legati tramite l'interazione con il proprio recettore di membrana GM1, e favorisce l'attivazione delle risposte immunitarie dirette contro tali antigeni.
Inoltre è stato dimostrato che la CTB agisce come un immunosoppressore, dal momento che è in grado di inibire l'attivazione delle linee cellulari monocito-macrofagiche e di sopprimere le risposte di tipo Th1.
Le nostre ricerche dimostrano che la rCTB previene parzialmente la maturazione di DC derivanti da monociti (MDDC) indotta da lipopolisaccaride (LPS) e ne diminuisce la produzione di IL-12p70 senza influenzarne la produzione di IL-10. Le DC pretrattate con CTB e stimolate con LPS sono così in grado di promuovere l'induzione di cellule T scarsamente proliferanti che mostrano un'aumentata produzione di IL-10 associata ad una ridotta produzione di interferon-γ (IFN-γ) e ad analoghi elevati livelli di trasforming growth factor-b (TGF-β), quando paragonati a quelli delle cellule di controllo.
Le cellule T così indotte sono capaci di sopprimere la proliferazione di cellule T autologhe attivate, tramite la produzione di fattori solubili, come dimostrano gli esperimenti effettuati mediante Transwell o con anticorpi bloccanti il recettore dell'IL-10 (IL-10R) ed il TGF-β. Tutte queste caratteristiche rendono le cellule T indotte da DC condizionate con rCTB simili alle Tregs di tipo 1 (Tr1) producenti IL-10.Antigen-non-specific innate immunity and antigen-specific adaptive immunity synergize to eradicate invading pathogens through the actions of immune cells and their effector proteins, including complement, antibodies, cytokines and cytolytic factors. Adaptive immune responses are induced, coordinated and regulated by dendritic cells (DC). DC initiate immunity by the activation of naïve B and T cells - the effector cells of the adaptive immune system - and by the stimulation of natural killer cells - the crucial cellular instigators of innate resistance. Besides linking innate and adaptive immunity, DC limit excessive, tissue-damaging immune responses in order to prevent autoimmunity and non-essential reactions to innocuous agents through their ability to induce antigen-specific unresponsiveness of lymphocytes in primary and secondary lymphoid tissues by mechanisms that include deletion and induction of regulatory T cells (Tregs). Given the central role of these antigen presenting cells in immunity and tolerance, they are ideal therapeutic targets for pharmacological modulation of immune responses. In the present study, we examined the possibility that recombinant CTB (rCTB) may affect human DC functions in response to toll-like receptor (TLR) stimulation and may induce the generation of DC with the capacity to generate Tregs. CTB - cholera toxin B subunit - is an efficient mucosal carrier molecule for the generation of immune responses to linked antigens, since it facilitates entry into the cell of the CTB-antigen complex by ligation of its surface receptor GM1. There is also good evidence that CTB acts as an immunosuppressant, as it is able to down-modulate human monocyte/macrophage cell line activation and to suppress Th1-type responses. Our findings show that rCTB partially prevents the lipopolysaccharide (LPS)-induced maturation process of monocyte-derived DC (MDDC) and decreases their interleukin-12p70 (IL-12p70) production with no relevant effect on IL-10 production. LPS-stimulated MDDC pre-treated with rCTB are able to promote the induction of low proliferating T cells, which show an enhanced IL-10 production associated with a reduced interferon-γ (IFN-γ) production and the same high levels of trasforming growth factor-β (TGF-β) as the control. These T cells suppress proliferation of activated autologous T cells. Transwell experiments and blockade of IL-10R and TGF-β showed that the immunomodulatory effect is mediated by soluble factors. Thus, T cells induced by rCTB-conditioned MDDC acquire a regulatory phenotype and activity similar to those described for IL-10 producing type 1 Tregs (Tr1).
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Witte, Amelie [Verfasser]. "The two cytosolic adapter proteins ADAP and SKAP55 : new insights into their role in T cell adhesion, migration and interaction with antigen-presenting cells / Amelie Witte." Magdeburg : Universitätsbibliothek, 2017. http://d-nb.info/1147834563/34.
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Cole, Lauren. "Primary Melanoma tumor immune contexture analysis: T regulatory cell to T effector cell ratio as related to MHC class II and GILT expression." Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/623292.
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A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Histopathologic examination of the tumor microenvironment demonstrates the presence of a vast repertoire of infiltrating lymphocytes and antigen presenting cells (APC’s). Recent studies establish a strong correlation between the tumor microenvironment cell composition and prognostic value in terms of cell type, location and ratio, referred to as a tumor’s immunoscore. More specifically, the relationship between T regulatory (Treg) cell to T effector (Teff) cell percentage predominates as a mechanism of tumor immune evasion. Further investigation of the factors influencing the development of Treg and Teff cells is therefore warranted. Gammainterferon‐inducible lysosomal thiol reductase (GILT) acts to influence antigenic processing and presentation by MHC class II cells, ultimately impacting lymphocyte development. Evaluation of the role of GILT expression in MHC class II+ APC’s with respect to Treg and Teff cell development in primary melanoma lesions, to our knowledge, has not been reported. Therefore our investigation focuses on elucidating a plausible relationship between GILT presence and Treg to Teff cell ratio. The aim of our study is to examine a possible association between GILT expression in APC’s and Treg:Teff cell ratio. We hypothesized GILT expression in melanoma cells would result in a decreased Treg to Teff ratio or an enhanced T cell‐mediated response. Our study included 17 de‐identified primary melanoma specimens previously stained and scored for Treg, Teff, CD8, MHC class II and GILT. Scoring was performed through identification of four areas per specimen with highest Treg and Teff cell density. These four areas were then averaged with ± standard deviation (SD). With use of landmark association, these four areas were identified and scored for MHC class II and GILT in APC’s and tumor cells with consideration to presence/absence, intensity and frequency of staining. Statistical significance was not reached relative to our hypothesized relationship of a decreased Treg to Teff cell ratio in the presence of GILT+ MHC class II. Similarly, we did not reach statistical significance when comparing individual cell types to GILT, MHC class II and GILT + MHC class. In our study, we were unable reach statistical significance relative to our proposed correlation between MHC class II and GILT presence leading to a decreased Treg to Teff cell ratio or enhanced T‐cell mediated immune response. A major limitation of our study included the small sample size leading to a probable type II error, prompting the need for further investigation of the factors influencing the Treg to Teff cell ratio within the melanoma tumor microenvironment on a larger scale.
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Chung, Yutein. "Identification of signaling pathways important for Borrelia burgdorferi-elicited IL-10 production by macrophages and their effects on suppressing antigen presenting cell immune responses." University of Toledo Health Science Campus / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=mco1308753897.
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Dübbel, Lena [Verfasser], Karl-Wilhelm [Akademischer Betreuer] Koch, and Edwin [Akademischer Betreuer] Bremer. "Characterization of the novel negative checkpoint regulator V-domain immunoglobulin-containing suppressor of T-cell activation (VISTA) on Antigen Presenting Cells / Lena Dübbel ; Karl-Wilhelm Koch, Edwin Bremer." Oldenburg : BIS der Universität Oldenburg, 2020. http://d-nb.info/1207469548/34.
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Thomas, Saskia. "Aberrant response of human myeloid dendritic cells to microbial stimuli in patients with inflammatory bowel disease." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://dx.doi.org/10.18452/16340.
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In zahlreichen Studien konnte an Mausmodellen gezeigt werden, dass dendritische Zellen eine wichtige Rolle im Rahmen der mukosalen Immunabwehr spielen. Eine unkontrollierte Aktivierung immunologischer Effektorzellen durch antigenpräsentierende Zellen ist die Folge, welche die Antigene der luminalen Flora folglich falsch erkennen und damit zu einer Schädigung des Gewebes führen. In der Arbeit wurden humane CD1c+CD11c+CD14-CD19- myeloide dendritische Zellen (mDCs) aus dem peripheren Blut und der intestinalen Mukosa von CED Patienten sowie von gesunden Probanden phänotypisch und funktionell näher charakterisiert. mDCs von Patienten reagieren auf LPS im Gegensatz zu DCs von Gesunden mit der Ausbildung eines aktivierten Phänotyps und der Sekretion pro-inflammatorischer Zytokine. Die Daten lassen vermuten, dass ihre tolerogene Rolle gestört ist und die Zellen so möglicherweise aktiv zum Entzündungsgeschehen durch eine Fehlreaktion auf die kommensale Flora beitragen. Es konnte gezeigt werden, dass zirkulierende mDCs von Erkrankten mehr LPS aufnehmen. Des Weiteren ist die Häufigkeit von mukosalen und aktivierten mDCs bei CED Patienten signifikant erhöht. Die vermehrte Häufigkeit von aktivierten mDCs in der entzündeten Mukosa ist ein Hinweis auf intestinales „homing“, also ein Wiedereinwandern der gereiften Lymphozyten in die Darmwand. Es ist bekannt, dass die Hefe Saccharomyces boulardii (Sb) eine Wirksamkeit bei entzündlichen sowie infektiösen Erkrankungen des Gastrointestinaltraktes hat. Kulturexperimente von mDCs mit Zellkulturüberständen von Sb (SbS) und LPS zeigten eine deutliche Reduzierung in der Expression von CD40 und CD80 sowie des Reifemarkers CD197. SbS reduzierte die Sekretion von TNF- und IL-6. Während es die Sekretion von IL-10 bei gesunden Probanden erhöhte, konnte bei CED Patienten eine leichte Abnahme verzeichnet werden. SbS vermindert die Proliferation von naïven T-Zellen in einer gemischten Lymphozytenreaktion mit gesunden mDCs signifikant.Various animal studies have provided insights that mucosal dendritic cells play a key role in this process. However, the specific function of certain dendritic cells in IBD is still unknown. Primary CD1c+CD11c+CD14-CD19- myeloid blood (mDCs) and mucosal DCs from IBD patients and healthy controls were compared. More mDCs from IBD patients exhibited an activated phenotype shown by expression of co-stimulatory molecules. mDCs from patients secrete higher levels of pro- and anti-inflammatory cytokines. Circulating mDCs from IBD patients take up more LPS and the frequency of mucosal mDCs and the number of activated, i.e. CD40 and CD80 expressing mucosal mDCs, is significantly greater in CED. The increased frequency of activated mDCs in the inflamed mucosa suggests intestinal homing of mDCs in acute stages of IBD. Further, the data suggests an aberrant LPS response of mDCs in patients suffering from IBD which results in an inflammatory phenotype. The most widely accepted hypothesis for the cause of IBD is a disturbed interaction of the host immune system with commensal microflora and other luminal antigens. The well controlled balance of the intestinal immune system is disturbed and luminal antigens like LPS gain access to the underlying mucosal tissue via the leaky barrier. It was investigated whether the yeast preparation Saccharomyces boulardii (Sb) modulates dendritic cell function which has shown efficacy in inflammatory and infectious disorders of the gastrointestinal tract. Culture experiments of mDCs in the presence of Sb culture supernatant (SbS) significantly reduced the expression of CD40 and CD80 as well as the DC maturation marker CD197 (CCR7) induced by the prototypical microbial antigen LPS. SbS reduced secretion of TNF- and IL-6, while the secretion of anti-inflammatory IL-10 increased. IBD patients showed also a reduction in their secretion level of IL-10. SbS inhibited proliferation of naïve T cells in a mixed lymphocyte reaction with healthy mDCs.
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Rodionova, Elena. "Developing anti-tumor vaccines: Antigens and Antigen-presenting cells." [S.l. : s.n.], 2006. http://digbib.ubka.uni-karlsruhe.de/volltexte/1000006088.
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Kawamura, Juliana Yuri. ""O efeito da ciclosporina A na população de células apresentadoras de antígenos em hiperplasia gengival medicamentosa"." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-04082006-094849/.
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A proposta do nosso estudo foi comparar o número de células apresentadoras de antígenos (CAAs) presentes em biópsias de gengivite (G) e de hiperplasia gengival induzida por ciclosporina (HGIC). Vinte e oito biópsias de pacientes com G e 14 biópsias de HGIC foram analisadas no epitélio de revestimento bucal (ERB), epitélio sulcular (ES) e no tecido conjuntivo (TC). O número de macrófagos (CD68+), de células de Langerhans (CD1a+) e de células dendríticas intersticiais (CDIs) (FXIIIA+) foi investigado por técnica imunoistoquímica. Células CD1a+/mm2 foram significantemente aumentadas na G quando comparada com HGIC, no TC, no ES e no ERB (p<0,05). Em contrapartida, o número de células CD68+ no TC e no ERB, e o número de células FXIIIA+/mm2 no TC foram aumentadas no grupo de HGIC (p<0,05). Ciclosporina A está relacionada com a diminuição de células de Langerhans. Podemos sugerir que este fato aumenta as infecções oportunistas, conseqüentemente, um maior número de macrófagos é necessário para combater os microorganismos.The aim of this study was to compare the number of antigen-presenting cells (APCs) observed in biopsies of gingivitis (G), and in cyclosporine-induced gingival overgrowth (CIGO). Twenty eight biopsies from patients with G, and 14 with CIGO were analyzed in oral epithelium (OE), sulcular/junctional epithelium (SJE), and connective tissue (CT). The number of macrophages (CD68+), Langerhanscells (CD1a+), and interstitial dendritic cells (FXIIIA+) was investigated by immunohistochemistry. CD1a+ cells/mm2 were significantly increased in G when compared with CIGO, in CT, in SJE, and in OE (p<0.05). In contrast, the number of CD68+ in CT, and in OE, and FXIIIA+ cells/mm2 in CT were increased in CIGO group (p<0.05). Cyclosporine is related with the diminution of Langerhans cells. We can suggest that this fact increase opportunistic infections, consequently, a greater number of macrophages is necessary in order to combat the microorganisms.
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Bachmann, Michael, Holger Bartsch, Biji T. Kurien, Robert Hal Scofield, Achim Temme, Knut Schäkel, Senming Zhao, et al. "A Novel Modular Antigen Delivery System for Immuno Targeting of Human 6-sulfo LacNAc-Positive Blood Dendritic Cells (SlanDCs)." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-186316.
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Background
Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767–777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.
Methodology/Principal Findings
Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells.
Conclusions/Significance
In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines.
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Baird, Allison Michelle. "Analysis of Low Zone Tolerance in Normal and B Cell-Deficient Mice." eScholarship@UMMS, 1996. https://escholarship.umassmed.edu/gsbs_diss/142.
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This thesis investigates the role of B cells as antigen-specific antigen-presenting cells (APC) in self tolerance to low concentrations of soluble self proteins and in acquired tolerance to low doses of soluble foreign protein antigens. Experiments were performed in normal and B cell-deficient animals, and tolerance induction was measured by T cell proliferation assays. T cell proliferation was reduced in B cell-deficient mice, indicating that B cells may be involved in efficient activation of naive T cells in response to protein antigen both in vivo and in vitro. To study acquired tolerance induced by low doses of soluble foreign protein antigen, normal and B cell-deficient adult mice were injected intravenously with repeated low doses (10 μg) of deaggregated ovalbumin (OVA), and then challenged with OVA in complete Freund's adjuvant. In animals treated with deaggregated OVA, the in vitro proliferative responses of LN T cells to OVA were significantly reduced, and production of the Th1 cytokine, IFN-γ, in response to OVA was lost. This occurred in both normal and B cell-deficient treated animals, indicating that B cell antigen presentation was not required for this phenomenon. B cells were also unnecessary for self tolerance of T cells to the transgenic self antigen, hen egg lysozyme (HEL), in a transgenic mouse strain with very low serum lysozyme concentration. Partial low zone tolerance induced by deaggregated, low-dose OVA was selective for the Th1 response, as measured by in vitro proliferation and IL-2 and IFN-γ production, because antibody responses of normal mice to this T cell-dependent antigen were largely unaffected. Both treated and untreated animals produced equivalent titers of anti-OVA antibodies, predominantly of the IgG1 and IgG2b isotypes, following challenge with OVA in complete Freund's adjuvant. Tolerance to low levels of the transgenic HEL self protein in mice expressing different MHC molecules was also addressed. Transgenic mice that were H-2b/b in the class II region were not tolerant to the transgenic self protein, whereas transgenic mice of the H-2b/k were tolerant.
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Kislat, Andreas [Verfasser], Bernhard [Gutachter] Homey, and Rainer [Gutachter] Kalscheuer. "The endogenous dual retinoic acid receptor agonist 9-cis retinoic acid downmodulates antigen-presenting cell functions to control immune responses / Andreas Kislat ; Gutachter: Bernhard Homey, Rainer Kalscheuer." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2018. http://d-nb.info/1164763253/34.
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MacKenzie, Jason Roderick, and Jason Mackenzie@ipaustralia gov au. "The Role of Eosinophils in the Regulation of CD4+ T helper 2 Regulated Inflammation." The Australian National University. The John Curtin School of Medical Research, 2004. http://thesis.anu.edu.au./public/adt-ANU20051007.121844.
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The eosinophil is a leukocyte whose intracellular mediators are considered to play a
central role in the pathogenesis of allergic diseases, including allergic asthma, allergic
rhinitis and atopic dermatitis, and which is also involved in immunological responses to
parasites. Eosinophil differentiation and maturation from bone marrow progenitors is
regulated by interleukin-5 (IL-5), which may be secreted by T helper 2 (Th2) T
lymphocytes, and is consistently upregulated in allergic conditions. Eotaxin is a potent
chemoattractant for circulating and tissue eosinophils, and the production of this
chemokine promotes eosinophil infiltration and accumulation within sites of allergic
inflammation.¶
Eosinophils obtained from inflammatory tissues and secretions display an altered
phenotype in comparison to peripheral blood eosinophils, with increased surface
expression of major histocompatibility complex (MHC) proteins and adhesion
molecules (Hansel et al., 1991), and migration across the microvascular endothelium
may also increase their capacity to generate an oxidative burst (Walker et al., 1993;
Yamamoto et al., 2000). Eosinophils are phagocytic cells, and have been shown to
present simple (no requirement for intracellular processing) and complex antigens to
MHC-restricted, antigen-specific T lymphocytes (Del Pozo et al., 1992; Weller et al.,
1993). Furthermore, eosinophils express the costimulatory molecules required for
effective antigen presentation (Tamura et al., 1996), and ligation of costimulatory
molecules on the eosinophil cell surface can induce the release of eosinophil derived
cytokines (Woerly et al., 1999; Woerly et al., 2002). Therefore the eosinophil may also
regulate immune responses.¶
To date, no studies have demonstrated the ability of eosinophils to modulate activated T
lymphocyte function via presentation of relevant antigen in the context of MHC class II
(MHC-II), concomitant with Th2 cytokine release. In the experiments described in this
thesis, murine eosinophils have been observed to rapidly migrate to sites of antigen
deposition within the airways mucosa of naïve mice, suggesting a potential role for this
granulocyte in the primary response to inhaled antigen. However, human allergic
diseases are often diagnosed after the establishment of allergic responses, and symptom
development. Therefore, a murine model of allergic airways disease (AAD) was used to
investigate the ability for eosinophils to participate as antigen presenting cells (APCs),
and thereby modulate activated T lymphocyte function both in vitro and in vivo.
Detailed histological analysis of the pulmonary draining lymph nodes following antigen
challenge in sensitised mice revealed a rapid infiltration of eosinophils into this tissue,
which preceded the accumulation of eosinophils in bronchoalveolar lavage fluid
(BALF). This suggested that eosinophils were preferentially translocating to the
draining lymph nodes following antigen challenge, and that the subsequent
accumulation of these cells in the BALF was a consequence of continued antigen
delivery to the lower airways.¶
Eosinophil trafficking to lymphoid tissue via the afferent lymphatics was substantiated
using electron microscopy of lymph node sections and the intravenous (i.v.) transfer of
fluorescently labeled eosinophils, which did not traffic to lymph nodes via the blood.
During the resolution of AAD, eosinophils were noted for their persistence in the
pulmonary draining lymph nodes. These observations suggested a continued modulation
of T cell function by lymph node dwelling eosinophils during AAD resolution,
particularly in light of recent observations for draining lymph node T cell proliferation
following instillation of antigen-pulsed eosinophils into the allergic mouse lung (Shi et
al., 2000).¶
To further investigate the antigen presenting capacity, eosinophils were obtained from
the BALF of mice with AAD, and their surface expression of MHC class II (MHC-II)
proteins and costimulatory molecules confirmed using flow cytometric analysis. The
ability to acquire and process complex antigen both in vitro and in vivo was also
confirmed using naturally quenching fluorescenated ovalbumin (OVA), which is
degraded into fluorescent peptides by the action of intracellular proteases. Thus,
eosinophil expression of the surface molecules necessary for effective antigen
presentation was confirmed, as was their ability to process complex antigen. Further
investigations revealed that eosinophils can present complex OVA antigen to CD4+ T
lymphocytes obtained from the allergic mouse, and to in vitro derived OVA-specific
Th2 cells. In the presence of exogenous antigen, eosinophils co-cultured with T
lymphocytes were able to induce Th2 cytokine production, and demonstrated an ability
for eosinophils to modulate T lymphocyte function in vitro.¶
The ability for eosinophils to act as antigen presenting cells in vivo was also
investigated. Eosinophils obtained from the antigen-saturated lungs of OVA sensitised
and challenged mice were transferred to the peritoneal cavities of naïve host mice.
When subsequently challenged with aerosolised OVA, eosinophil recipients developed
a pulmonary eosinophilia similar to that of OVA sensitised and challenged mice. To
validate this finding, the experimental procedure was altered to accommodate the use of
non-allergy derived eosinophils, which were pulsed with OVA in vitro, prior to transfer
into naïve recipients. When subsequently challenged with aerosolised OVA, eosinophil
recipients developed a peripheral blood and pulmonary eosinophilia, and stimulation
with OVA induced IL-5 and IL-13 cytokine production from pulmonary draining lymph
node cells. Notably, the AAD induced by transfer of antigen pulsed eosinophils did not
induce detectable OVA-specific IgG1, which may be attributed to the lack of soluble
antigen required for B cell antibody production.¶
During the course of these investigations, an OVA T cell receptor (TCR) transgenic
mouse (OT-II) was procured with a view to defining the interaction between eosinophils
and activated T lymphocytes (Barnden et al., 1998). Despite having specificity for the
OVA323-339 peptide, an immunodominant epitope that skews naïve T cell responses
towards Th2 cytokine release (Janssen et al., 2000), T lymphocytes from the OT-II
mouse preferentially secreted IFN-γ in response to stimulation with either OVA peptide
or OVA. These mice were further characterised in a mouse model of AAD, and found to
be refractory to disease induction and progression, which may be attributed to
significant IFN-γ secretion by transgenic CD4+ T lymphocytes during antigen
sensitisation. Indeed, these cells were noted for their ability to attenuate pulmonary
eosinophilia when transferred to OVA sensitised and challenged wild type mice,
although serum OVA-specific IgG1, peripheral blood eosinophilia levels and airways
response to methacholine challenge remained intact.¶
Knowledge of the biased Th1 phenotype in naïve OT-II provided a unique opportunity
to investigate the fate of T lymphocytes bearing high affinity OVA-specific TCRs
following neonatal antigen exposure to soluble OVA. In a previous study, subcutaneous
(s.c.) administration of soluble OVA to wild type neonatal mice was suspected to have
deleted OVA-specific T cells from the T cell repertoire (Hogan et al., 1998a). Using
flow cytometry and TCR specific antibody, the delivery of s.c. OVA to OT-II neonates did not alter transgenic T cell populations in adult mice. Instead, it was surprising to
find a skewing towards the Th2 phenotype and loss of IFN-γ secretion following OVA
sensitisation and challenge in adult mice. A mechanism for this reprogramming of the
transgenic T cell from the Th1 to a Th2 phenotype following OT-II neonatal exposure
to soluble OVA is proposed, and further experimentation may validate this hypothesis.¶
In conclusion, eosinophils residing in the allergic lung have the capacity to interact with
activated T cells, both within this tissue and the draining lymph nodes. Despite their
relative inefficiency as antigen presenting cells (Mawhorter et al., 1994), eosinophils
may participate en masse in the serial triggering of activated TCRs, and provide
appropriate costimulatory signals that modulate T lymphocyte function. Through the
elaboration of Th2 cytokines and stimulation of T cell proliferation, antigen presenting
eosinophils may transiently prolong or exacerbate the symptoms of allergic diseases.
Alternatively, eosinophils presenting relevant antigens may inhibit T cell activity via
degranulation, and such activity has recently been observed in a parasite model (Shinkai
et al., 2002). Finally, experiments in the OT-II mouse have provided valuable
information to suggest that therapies designed to modulate eosinophil numbers in
allergic tissues through the secretion of opposing cytokines such as IFN-γ, may be of
limited benefit. The results shown here suggest that airways dysfunction remains intact
despite significantly reduced pulmonary eosinophilia
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Bachmann, Michael, Holger Bartsch, Biji T. Kurien, Robert Hal Scofield, Achim Temme, Knut Schäkel, Senming Zhao, et al. "A Novel Modular Antigen Delivery System for Immuno Targeting of Human 6-sulfo LacNAc-Positive Blood Dendritic Cells (SlanDCs)." PLOS, 2011. https://tud.qucosa.de/id/qucosa%3A29020.
Full textAbstract:
Background
Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767–777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.
Methodology/Principal Findings
Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells.
Conclusions/Significance
In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines.
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Proust, Alizé. "Etude du transfert du VIH-1 des cellules présentatrices d'antigènes aux lymphocytes T CD4 primaires et inhibition par les anticorps neutralisants." Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ107/document.
Full textAbstract:
Les cellules présentatrices d'antigènes (APCs) présentes dans les muqueuses comptent parmi les première cibles du VIH-1 et participent à sa dissémination dans l'organisme. Durant ma thèse, j'ai étudié le transfert du VIH des macrophages (Mφ) et des cellules dendritiques (DCs) aux lymphocytes T. J'ai montré que ces APCs transfèrent efficacement le virus aux lymphocytes par le biais de différents mécanismes: transfert direct en trans dans les coculture Mφ/T, et transfert en cis (suite à la production de nouveaux virions) dans les DCs/T. Ces deux modes de transfert sont inhibés par les anticorps neutralisants (AcN). De manière intéressante, certains AcN anti-gp120 inhibaient plus efficacement le transfert du VIH dans les cocultures Mφ/T que dans les cocultures DCs/T et l'infection des cellules T par le virus libre. Ces résultats suggèrent que les APCs participent activement au transfert et à la dissémination du VIH et que les AcN sont capable d'inhiber ces différents modes de transfertAntigen-presenting cells (APCs) present at mucosal sites are among the first HIV-1 target cells and contribute to the spread of infection. During my thesis, I studied HIV transfer from macrophages (Mφ) and dendritic cells (DCs) to CD4-T lymphocytes. I showed that APCs were able to efficiently transfer HIV particles to lymphocytes, but through different mechanisms: Mφ rapidlytransferred HIV by direct trans-transfer, whereas DCs were mainly implicated in cistransfer (after production of de novo HIV). Moreover, I have demonstrated that these two modes of transfer were inhibited by neutralizing antibodies (NAb) in both type ofcocultures. Very interestingly, I showed that anti-gp120 NAb inhibit more efficiently HIV transfer in Mφ/T than in DCs/T cocultures and T cells infection by free viral particles. These findings highlight the major contributions of various mucosal target cells in HIV transfer and demonstrate the potent role of NAb on inhibition of cell-to-cell transfer
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Winchester, Christopher Charles. "The roles of Hsp70 proteins in antigen processing and presentation." Thesis, University of Oxford, 1997. http://ora.ox.ac.uk/objects/uuid:567dff45-08ce-43b4-b011-d08afea42f76.
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The ability of members of the hsp70 family to bind to peptides in vivo and in vitro suggests that they may be involved in the processing of antigens for binding to Major Histocompatibility (MHC) class I and/or class n molecules. The aims of this thesis have been to provide evidence for the involvement of hsp70s in antigen processing and to characterise the binding of peptides by hspTOs by structural and functional studies. Firstly, the peptide-binding domains of two hsp70s, hsp70hom and PBP74, were expressed in isolation from the rest of the molecule for structure determination. Both of these hsp70s were implicated in antigen processing: hsp70hom in the class I pathway, due to its cytoplasmic localisation and constitutive expression, and the presence of its gene in the MHC; and PBP74 in the class n pathway because published work indicated that it was localised to endosomes and that antibodies against it inhibited antigen processing. The expression and purification of both peptide-binding domains was very successful, and one dimensional NMR experiments indicated that they were folded. However, it was not possible to determine their structures by NMR spectroscopy or X-ray crystallography because they aggregated in solution at high concentrations. Instead, the structure of the C-terminal region of hsp70hom, which includes its peptidebinding domain, was modelled based on the known structure of the equivalent portion of dnaK, the hsp70 of E.coli. The structure of hsp70hom is predicted to be very similar to that of dnaK, and modelling studies suggest that it is likely to bind peptides in a closely related fashion. The modelling of complexes between hsp70hom and two peptides suggest that the peptide-binding groove is very versatile, accounting for the broad peptide-binding specificity of hsp70s. The interactions of hsp70hom and PB74 with peptides were investigated using plate binding assays and isothermattitration calorimetry. A biotinylated peptide bound to the peptide-binding domain of hsp70hom, immobilised in plastic wells, with a Kd of <25 μM, which is within the range of Kds reported for other hsp70-peptide complexes (0.1-100 μM). In solution, isothermal titration calorimetry showed that the binding of peptides to the peptide-binding domains of hsp70hom and PBP74 was likely to be entropically rather than enthalpically driven, and, therefore, the interactions involved are likely to be predominantly hydrophobic. Secondly, PBP74, an hsp70 thought to be involved in the class II antigen processing pathway in endosomes, was localised by immunofluorescence microscopy. It was shown to be a mitochondrial protein, and is, therefore, unlikely to be involved in antigen processing. The presence of other members of the hsp70 family in lysosomes purified from a B cell line by Percoll density gradient centrifugation was investigated using antibodies that reacted with many Afferent members of the hsp70 family. No hsp70s were detected in these late endocytic compartments, even after heat shock or serum starvation. However, the presence of an hsp70 in endosomes, or of a member of this family not detected by the antibodies used, in lysosomes, cannot be ruled out. A third approach investigated the induction of the three hsp70 genes found in the MHC by four cytokines. The hsp70-l and hsp70-2 genes are induced at the mRNA level by IFN-γ and IL- 1, while TNF induces hsp70-2 alone. This data supports a role for the heat-inducible hsp70 in MHC class I antigen processing, as it appears to be coregulated with known members of this antigen processing pathway. The expression of hsp70hom was unaffected by any of the four cytokines examined. In addition, the mitochondrial hsp70 (which is not encoded in the MHC) appears to be induced by IFN-γ at the protein level. The research presented in this thesis provides a greater understanding of the peptide-binding properties of two hsp70s. Further work is necessary to show conclusively whether any of the hsp70s is involved in antigen processing.
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Misztela, Dominika. "The differential effects of CD80 and CD86 in helper T lymphocyte activation." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670088.
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Dupel, Estelle. "Développement de nouvelles stratégies d'immunothérapie cellulaire anti-tumorale basées sur la construction de cellules présentatrices d'antigènes artificielles." Thesis, Normandie, 2018. http://www.theses.fr/2018NORMR002.
Full textAbstract:
L’immunothérapie basée sur le transfert de lymphocytes T (LT) spécifiques de la tumeur est une approche prometteuse contre le cancer. Pour activer et amplifier de tels LT, principale étape limitante de cette approche, des cellules présentatrices d’antigène artificielles (CPAA) ont été développées au laboratoire. Ces CPAA ont été construites à partir de fibroblastes murins NIH/3T3 transduits à l’aide de vecteurs gammarétroviraux afin d’exprimer les principaux éléments nécessaires à l’activation de LT humains. Ces CPAA nous permettent d’obtenir des LT mémoires souches (TSCM : CD95+CD45RA+CD62L+CCR7+), LT très peu différenciés récemment identifiés chez l’homme. Ces TSCM ont été décrits comme étant du plus grand intérêt pour l’immunothérapie en raison de leur capacité d’auto-renouvellement et de leur faculté à se différencier en LT effecteursefficaces. Pour optimiser l’amplification de TSCM spécifiques, nous avons notamment étudié les effets sur les LT de l’expression de différentes molécules de costimulation par nos CPAA (CD80, CD70 et 4-1BBL). Les protéines MART-1 et MELOE-1, surexprimées dans les mélanomes, ont été utilisées comme antigènes modèles pour ces travaux. Les CPAA CD80+CD70+ et CD80+CD70+4-1BBL+ sont les plus prometteuses pour maintenir le phénotype des TSCM. Une étude exhaustive des CPAA CD80+CD70+ a montré que nous pouvions obtenir un plus grand nombre de TSCM fonctionnels spécifiques de MART-1 et de MELOE-1 de manière reproductible avec ces CPAA. Dans une seconde étude, nous avons pu montrer que les CPAA CD80+CD70+4-1BBL+ permettaient d’obtenir le plus grand nombre de LT spécifiques fonctionnels et très peu différenciés après purification et restimulation de LT spécifiques stimulés une première fois par les CPAA CD80+CD70+. Ces travaux devraient nous permettre, après le développement d’un modèle murin, de proposer de nouvelles stratégies d’immunothérapie basées sur l’obtention grâce à nos CPAA optimisées de LT spécifiques anti-tumoraux capables d’assurer une protection à long terme aux patientsImmunotherapy based on the transfer of tumor-specific T lymphocytes (TLs) is a promising approach against cancer. To activate and amplify such TLs, main limiting step of this approach, artificial antigen presenting cells (AAPCs) have been developed in the laboratory. These AAPCs have been constructed from NIH/3T3 murine fibroblasts transduced with gammaretroviral vectors to express the principal elements required to activate human TLs. With these AAPCs, we can obtain anti-tumor stem cell memory TLs (TSCM: CD95+CD45RA+CD62L+CCR7+), which are very limitedly differentiated TLs recently identified in humans. These TLs have been recently described as cells of great interest for immunotherapy because of their self-renewal capacity and their ability to differentiate into effective effector TLs. To improve the amplification of specific TSCM, we notably studied the effects on TLs of the expression of different co-stimulatory molecules by our AAPCs (CD80, CD70 and 4-1BBL). MART-1 and MELOE-1, proteins that are overexpressed in melanoma, were used as model antigens in this work. CD80+CD70+ and CD80+CD70+4-1BBL+ AAPCs appear to be the most promising ones for maintaining a TSCM phenotype. An exhaustive study of CD80+CD70+ AAPCs showed that we could reproducibly get greater numbers of MART-1- and MELOE-1-specific functional TSCM with these AAPCs. In another study, we have shown that CD80+CD70+4-1BBL+ AAPCs enabled us to get the greatest number of functional and very limitedly differentiated specific TLs after purification and restimulation of specific TLs stimulated first with CD80+CD70+ AAPCs. This work should allow us, after the development of a murine model, to propose new immunotherapy strategies based on the possibility of obtaining with our optimized AAPCs anti-tumor specific TLs capable of ensuring patient long term protection
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Brooks, C. F. "Antigen presenting cells in human peripheral blood." Thesis, University of Manchester, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234349.
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Eynon, Elizabeth E. "Small B Cells as Antigen Presenting Cells in the Induction of Tolerance to Soluble Protein Antigens: A Dissertation." eScholarship@UMMS, 1991. https://escholarship.umassmed.edu/gsbs_diss/185.
Full textAbstract:
This thesis proposes a mechanism for the induction of peripheral tolerance to protein antigens. I have investigated the mechanism of tolerance induction to soluble protein antigens by targeting an antigen to small, resting B cells. For this purpose I have used a rabbit antibody directed at the IgD molecule found on the surface of most small, resting B cells but missing or lowered on activated B cells. Intravenous injection of normal mice with 100 μg of an ultracentrifuged Fab fragment of rabbit anti-mouse IgD (Fab anti-δ) makes these mice profoundly tolerant to challenge with nonimmune rabbit Fab (Fab NRG) fragments. This tolerance is antigen specific since treated mice make normal responses to an irrelevant antigen, chicken immunoglobulin (Ig). Fab fragments of rabbit Ig (rabbit Fab) not targeted to B cells do not induce tolerance as well as Fab anti-δ. Evidence suggests that the B cells must remain in a resting state for tolerance to be induced, since injection of F(ab)'2 anti-δ does not induce tolerance. Investigation of the mechanisms of the tolerance, by adoptive transfer, have shown that rabbit Fab specific B cell function has been impaired. The major effect however is in helper T cell function, as shown by adoptive transfer and lack of help for a hapten response. In vitro proliferation experiments show that the T cell response has not been shifted toward activation of different T cell subsets which do not help Ig production, nor is there any change in the Ig isotypes produced. Suppression does not appear to be the major cause of the helper T cell defect as shown by cell mixing experiments. This work shows that an antigen targeted to small B cells can induce tolerance to a soluble protein antigen, and suggests a role for small B cells in tolerance to self-proteins not presented in the thymus.
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Zheng, Biao. "Inductive interactions between antigen presenting cells and T cells." Thesis, Open University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314796.
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Jacquemin, Clément. "Modulation de la balance lymphocytaire T régulatrice et effectrice dans deux modèles de maladies auto-immunes." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22050.
Full textAbstract:
Le respect de l’équilibre entre lymphocytes T effecteurs auto-réactifs et lymphocytes T régulateurs (LTreg) est primordial dans le maintien de la tolérance aux antigènes du soi. Les partenaires cellulaires et les mécanismes moléculaires impliqués dans la rupture de l’équilibre de cette balance ne sont pas ou peu connus dans les maladies auto-immunes. Ainsi, les travaux décrits dans cette thèse portent sur le dérèglement de la balance T effecteurs/ Treg dans deux modèles de maladies auto-immunes chez l’homme: le lupus érythémateux systémique et l’anémie hémolytique auto-immune (AHAI). Nous montrons une augmentation de l’expression de la molécule de costimulation OX40L (CD252, TNFSF4) à la surface des cellules présentatrices d’antigène circulantes et infiltrant les tissus chez les patients lupiques. Cette augmentation est corrélée à l’activité de la maladie chez l’adulte comme chez l’enfant. Elle a pour conséquence l’induction de lymphocytes T effecteurs de type Tfh (T follicular helper) et le blocage des fonctions suppressives des Treg, deux acteurs majeurs dans la physiopathologie du lupus. Dans le second projet, nous montrons une augmentation de la proportion de T8reg circulants chez les patients affectés d’une AHAI à anticorps chauds en phase de rémission. Ces Treg expriment le CD25, le FoxP3 et exercent leur fonction suppressive par un mécanisme faisant intervenir l’IL10. De faibles doses d’IL-2 permettent l’expansion de cette population cellulaire in vitro. Ces résultats apportent de nouvelles connaissances dans la physiopathologie de ces deux maladies et offrent des perspectives thérapeutiques potentiellesRespect of the balance between autoreactive T cells and regulatory T cells (LTreg) is important to maintain tolerance to self-antigens. Cellular partners and molecular mechanisms involved in the disruption of this balance are not or little known in autoimmune diseases.Thus, the work described in this thesis focuses on the disruption of the T effector/ Treg balance in two models of human autoimmune diseases: systemic lupus erythematosus and autoimmune hemolytic anemia (AIHA). We show an increased expression of the OX40L (CD252, TNFSF4) costimulatory molecule at the surface of both circulating and tissues-infiltrating antigen presenting cells in SLE patients. OX40L expression is correlated with disease activity in adults and in children and results in Tfh (follicular helper T) effector cells induction and Treg suppressive functions inhibition, two key mechanisms in the pathogenesis of lupus. In the second project, we show an increase of the circulating T8reg proportion in patients with a warm AIHA in a non-active state. These Treg express CD25, FoxP3 and exert their suppressive function by a mechanism involving IL-10. Low-dose IL-2 allows the expansion of this cell population in vitro. These results provide new insights into the pathophysiology of these diseases and offer potential therapeutic perspectives
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Vicente-Suarez, Ildefonso. "Immunomodulatory role of flagellin in antigen-presenting cells." [Tampa, Fla] : University of South Florida, 2007. http://purl.fcla.edu/usf/dc/et/SFE0002201.
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McCormick, P. Andrew. "Interaction of bovine antigen-presenting cells with mycobacteria." Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435849.
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Kalupahana, Ruwani Sagarika. "Interaction of Salmonella typhimurium with antigen presenting cells." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620666.
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