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Carnathan, Diane Gail Vilen Barbara J. "Dendritic cell regulation of B cells." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1200.
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Thesis (M.S.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Mar. 26, 2008). "... in partial fulfillment of the requirements for the degree of Master of Science in the Department of Microbiology and Immunology, School of Medicine." Discipline: Microbiology and Immunology; Department/School: Medicine.
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Liu, Hao. "Dendritic cell development directed by stromal cells." Thesis, University of York, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516409.
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Hansell, C. A. H. "Identification of avian dendritic cells." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603659.
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The aim of this study was to identify dendritic cells in the chicken through the development of a set of markers and probes to potential dendritic cell markers in the chicken. In the absence of markers to avian dendritic cell markers published sequence databases were used to identify three candidate markers that showed significant homologies to CD83, fascin and DEC205 all potential dendritic cell markers in humans and mice. These markers were chosen for the following reasons: CD83 is currently the best marker of mature human and murine dendritic cells; fascin-1 is an actin bundling protein highly conserved between species, with expression restricted in leukocytes to dendritic cells; and DEC205 is a C-type lectin whose expression is also restricted to dendritic cells. CD83 was expressed in immunologically relevant tissues, had low levels of expression in the bursa and was not detectable on endothelial cell types. Based upon these distributions, CD83 was selected as the most suitable marker of dendritic cells in the chicken and an anti-chicken CD83 polyclonal serum and monoclonal antibodies were used to assess the expression of CD83 at the protein level. A map of CD83 expression was created using immunohistochemistry techniques upon a variety of tissues including spleen thymus and bursa derived from out-bred chickens and specific pathogen free chickens. This data revealed that whilst some aspects of CD83 immunobiology were conserved such as the upregulation of CD83 expression under inflammatory conditions, the distribution of CD83+ cells was uniquely distributed amongst the B cell areas of the chicken immune system in contrast to the T cell associated distribution of humans and mice. The expression of CD83 by specific cellular lineages was determined using commercially available lineage specific monoclonal antibodies and two-colour fluorescent microscopy. This established a dendritic cell type with features that are unique to the chicken.
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Jones, Lucy Helen. "Alternative activation of dendritic cells." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8284.
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The alternative activation of macrophage populations by Interleukin-4 (IL-4) is well characterised. Alternatively activated macrophages (AAM) express high levels of the arginine converting enzyme arginase-1, and express a plethora of IL-4 driven molecules including the resistin like molecule alpha (RELMα) and the chitinase like molecule Ym1/2. Dendritic cells (DCs) are the professional antigen presenting cells (APC) of the immune system, responsible for the detection of invading pathogens, secretion of cytokines and the subsequent activation of T-cells. This thesis addresses whether IL-4 is able to ‘alternatively activate’ DCs both in vitro and in vivo, in a manner similar to that of AAM. The impact of IL-4 on DC and macrophage activation was compared and contrasted, and it was confirmed for the first time that IL-4 can alternatively activate DCs, inducing high level expression of a range of alternative activation associated markers including RELMα, Ym1/2, CCL24 and dectin-1, with the exception of arginase. DCs were significantly more capable at the in vivo priming of T-cell responses in the context of both Th1 and Th2 polarising antigens than similarly exposed macrophages, confirming their superior capacity as APC. The requirements for DC IL-4Rα expression were assessed, and IL-4 responsiveness was found to be required for the optimal induction of Th1 responses. Conversely, selective loss of only one facet of the IL-4 response, namely RELMα expression, limited the ability of IL-4 exposed DCs to induce the regulatory cytokine IL-10 both in vitro and in vivo. Furthermore, alternatively activated DCs (AADCs) were found in the spleen following 8 weeks of infection with the parasitic trematode Schistosoma mansoni, highlighting a role for DC alternative activation in a disease setting. IL-4 was shown to induce expression of the vitamin A converting enzyme aldehyde dehydrogenase, and the product of such activity, retinoic acid (RA), was found to promote the expression of RELMα in IL-4 exposed DCs. Aldehyde dehydrogenase activity was found to inversely correlate with DC expression of Ym1/2 and inhibition of RA signalling limited IL-4 driven RELMα and promoted Ym1/2.
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Rigby, Rachael Jane. "Intestinal dendritic cells : characterisation of the colonic dendritic cell population and identification of potential precursors." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407134.
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Javorovic, Miran. "T-Cell Stimulation by Melanoma RNA-Pulsed Dendritic Cells." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-30569.
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Kavikondala, Sushma. "Dendritic cell and B cell interactions in systemic lupuserythematosus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39793710.
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Kwong, Amelia. "Crosstalk Between T Cells, Dendritic Cells, Cytokines, and Chemokines." Thesis, The University of Arizona, 2010. http://hdl.handle.net/10150/146198.
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T cells that came into contact with mature and immature dendritic cells had an overall reduction in gene expression in IL10, IL12, IL23, ICOS, TGFB, TNFA, PD1, TBET, GATA3, FASL, PERF, FOXP3, and CTLA4. T cells stimulated with immature dendritic cells had the most consistent results in decreasing gene expression in all the genes tested. T cells in contact with mature dendritic cells had mostly a decrease in gene expression, but in IFNG and Granzyme there was an increase in gene expression. However, when adding additional stimuli such as interferon(IFN) or hydroxychloroquine (HCQ) gene expression increased in all of the markers except for TGFB, PERF, and IL12. This leads me to believe that crosstalk is occurring between dendritic cells and T cells. This crosstalk could direct the particular cells to perform specialized functions, which can explain the increase and decrease of the markers tested. In addition, interferon and hydroxychloroquine seems to hyper-stimulate most markers to create an up regulation of gene expression.
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Lee, Michael Hweemoon. "Modulators of Dendritic Cells and B cells in Lupus." Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/565007.
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Microbiology and ImmunologyPh.D.
Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies directed against ubiquitous self-antigens, many of which are nuclear autoantigens like dsDNA and chromatin (Pisetsky, 2016), and by elevated type I interferons (IFN) (Hooks et al., 1979; Weckerle et al., 2011), a family of pro-inflammatory cytokines that have antiviral activity (Pestka et al., 2004). Microarray analysis of peripheral blood mononuclear cells (PBMC) from SLE patients discovered the increased expression of IFN-responsive genes that was named the IFN Signature (Baechler et al., 2003a; Bennett et al., 2003b; Crow et al., 2003). Genome wide association studies indicate a clear genetic component in lupus pathogenesis (Chung et al., 2011; SLEGEN et al., 2008) and murine models of SLE confirm genetic drivers of the disease (Morel, 2010; Morel et al., 2000). However, the concordance of SLE in monozygotic twins is only 30-40% (Connolly and Hakonarson, 2012), while the inc
Temple University--Theses
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Milioti, Natalia. "Immunomodulation of atherosclerosis using dendritic cells." Thesis, University of Surrey, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608344.
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Inflammation plays a crucial role in atherosclerotic plaque generation/progression. Dendritic cells (DCs). cellular immune-response components linking innate and adaptive immune systems, have been found in atherosclerotic plaques. In this study, Des were examined as a possible therapeutic tool to modulate the inflammatory immune response underlying plaque formation. Apolipoprotein (apo) B-100 derived antigens are believed to modulate humoral immune responses to achieve atheroprotection, but their role in cellular immunity remains unclear. Therefore, one objective was to characterise the immunomodulatory effect of apoB-100-derived peptides (P2, P45, P210) on immature DCs (iDCs) and naive T lymphocytes ill vitro. iDCs were generated from bone-marrow progenitor-cells of male apoE-'- mice. Peptide up-take and processing was studied by confocal microscopy after 6h, 2411 and 48h. Peptide P45 was found in the endolysosomal compartments, co-localising with MHC-I and :MHC-II antigen-presenting complexes. The phenotypic and differentiation characteristics of P2, P45 and P21O-Joaded DCs were studied by flow cytometry, and cytokine and matrix metalloproleinase production by PCR/ELISA after 48h. Proliferation and differentiation of T lymphocytes driven by peptide-loaded DCs was also studied. Peptide-loaded DCs displayed a tolerogenie phenotype similar to that of unloaded, iDCs, and inhibited CD4+ proliferation induced by mature DCs when co-cultured. My results suggest that the protective effect of the peptides could be mediated by DCs presenting them to T cells. A second objective was to examine the effect of vaccination with tolerogenic DCs (toIDCs), generated in vitro through incubation with IL-10 and TGF-β for 6 days, on atherosclerotic progression in apoE-/- mice. This showed that immunisation with tolDCs increased the number of CD8+CD25'FoxP3+ T regulatory cells as well as secretion of IL-l0 within the spleen of immunised mice. IL- l0 levels were also elevated in the serum, while cholesterol levels were reduced, although plaque size remained unchanged. These results provide new insights for treatment and prevention of atherosclerosis through vaccination.
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Marín, Millán Eros Alexandre. "Novel mechanisms in tolerogenic dendritic cells." Thesis, Nantes, 2018. http://www.theses.fr/2018NANT1032/document.
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Les recherches menées sur les cellules dendritiques tolérogènes au cours des 20 dernières années ont abouti à leur application thérapeutique dans plusieurs essais cliniques. Parmi ces essais, notre équipe est pionnière en transplantation rénale en réalisant de la thérapie cellulaire à l’aide des cellules dendritiques tolérogènes autologues générées avec une faible dose de GM-CSF (ATDC). Nos études précliniques ont démontré que ces cellules sont capables d’augmenter la survie de différentes allogreffes chez les rongeurs et n'induisent pas d'effets indésirables chez les primates. Lors de ma thèse, j’ai montré que les ATDC humaines présentent une faible expression de molécules co-stimulatrices, ne maturent pas et inhibent la prolifération des cellules T. De plus, les ATDC présentent un phénotype, un profil transcriptomique et un métabolisme particuliers qui les dissocient de d’autres cellules myéloïdes. Afin de déterminer les mécanismes suppressifs de ces cellules, j’ai réalisé différents tests démontrant que les ATDC sont capables d’inhiber la prolifération des cellules T CD4+, d’altérer la production d'IFN et IL- 17A et d’induire la différenciation CD4+CD25+FoxP3hiTreg par des mécanismes indépendants du contact cellulaire. L'analyse du surnageant des ATDC (ATDC-SN) a révélé que ces cellules produisent une forte concentration de lactate,qui est en partie responsable de leur effet immunosuppresseur. Cette étude a permis de démontrer que la sécrétion d’acide lactique est un nouveau mécanisme des ATDCs et ouvre une nouvelle perspective de thérapie cellulaire associée à la production de petites moléculesThe research focused on tolerogenic dendritic cells during the last 20 years has culminated on their therapeutic application in several clinical trials. Among these trials, our team is currently conducting the first trial in the context of kidney transplantation using tolerogenic dendritic cells generated with low dose of GM-CSF (ATDC). We previously reported that Tol-BMDC generated with this protocol prolong thesurvival of different allografts in rodent models and do not induce adverse effects in nonhuman primates. In this work I demonstrated that ATDC derived from human monocytes, similarly to their bone marrow equivalent, display a low expression of costimulatory molecules, do not maturate and impair T-cell proliferation. Interestingly, ATDC display a particular phenotype, transcriptomic profile and metabolism comparing to other myeloid cells. In order to determine the suppressive mechanisms of these cells, I performed different assays demonstrating that ATDC impaired CD4+T-cells proliferation and IFN and IL-17A production, and induced de novo CD4+CD25+FoxP3hiTreg by contactindependent mechanisms. The analysis of ATDC supernatant (ATDC-SN) revealed a high concentration of lactate. I demonstrated that this lactate production is in part responsible of ATDC immunosuppressive effects. This study allowed to demonstrate that lactic acid secretion is a novel mechanisms displayed by ATDC and opens a new perspective of cell therapy based on the production of small molecules
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Rivera, Cifuentes Claudia Andrea. "Intraepithelial dendritic cells : origin and function." Electronic Thesis or Diss., Université Paris Cité, 2021. http://www.theses.fr/2021UNIP5167.
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Les cellules dendritiques (CDs) patrouillent les tissus et transportent les antigènes vers les ganglions lymphatiques pour initier des réponses immunitaires adaptatives. Au sein des tissus, les CDs constituent une population cellulaire complexe composée de sous-types distincts pouvant présenter différents états d'activation et fonctions. La façon dont les signaux tissulaires orchestrent la diversification des CDs reste insaisissable. La Lamina Propria (LP) de l'intestin grêle (IG) est enrichie par une population particulière de cCD2 exprimant les intégrines CD103 et CD11b. Une fraction de ces cellules peut transmigrer dans l'épithélium à l'état d'équilibre et en proportion plus élevée lors d'une infection. Cependant, les conséquences d'un tel événement sur l'identité et le destin de ces cellules sont inconnues. En utilisant l'analyse de séquençage d'ARN unicellulaire, nous avons constaté que la transmigration des CDs CD103+CD11b+ dans l'épithélium modifie profondément leur profil transcriptomique caractérisé par une baisse d'expression des gènes inflammatoires et une augmentation d'expression des gènes associés à l'activité antimicrobienne. Nous avons ensuite décrit que l'intestin grêle comprend deux pools de cCD2s provenant de précurseurs de préCDs communs : (1) cCD2s CD103+CD11b+ de la LP qui sont des cellules pro-inflammatoires de type mature et (2) des cCD2s intraépithéliales qui présentent un phénotype similaire à celui des CDs immatures induisant des propriétés tolérogènes des lymphocytes T. Ce phénotype résulte de l'action de l'acide rétinoïque d'origine alimentaire (ATRA), qui améliore la contractilité de l'actomyosine et favorise la transmigration des cCD2s de la LP vers l'épithélium. Les cCD2s sont alors influencées par des indices environnementaux spécifiques à l'épithélium comprenant l'ATRA lui-même ainsi que le composant muqueux Muc2. Par conséquent, en atteignant des niches sous-tissulaires distinctes, les CDs peuvent exister sous forme de cellules immatures et matures dans le même tissu, révélant un nouveau mécanisme de diversification fonctionnelle des CDsDendritic cells (DCs) patrol tissues and transport antigens to lymph nodes to initiate adaptive immune responses. Within tissues, DCs constitute a complex cell population made of distinct subsets that can exhibit different activation states and functions. How tissue-specific cues orchestrate DC diversification remains elusive. Particularly, the small intestine (SI) Lamina Propria (LP) is enriched in a peculiar population of cDC2s expressing the integrins CD103 and CD11b. Interestingly, a fraction of these cells can transmigrate into the epithelial layer both at steady state and in higher proportion upon infection. However, the consequences of such event on the identity and fate of these cells is unknown. By using single cell RNAseq analysis, we found that their epithelial colonization deeply modifies their transcriptomic profile, downregulating inflammatory genes expression and stimulating the transcription of antimicrobial genes. We then further described that the small intestine includes two pools of cDC2s originating from common preDC precursors: (1) lamina propria CD103+CD11b+ cDC2s that are mature-like pro-inflammatory cells and (2) intraepithelial cDC2s that exhibit an immature-like phenotype and induce tolerogenic T lymphocyte properties. Intraepithelial cDC2 phenotype results from the action of food-derived retinoic acid (ATRA), which enhances actomyosin contractility and promotes LP cDC2 transmigration into the epithelium. There, cDC2s are imprinted by environmental cues including ATRA itself and the mucus component Muc2. Hence, by reaching distinct sub-tissular niches, DCs can exist as immature and mature cells within the same tissue, revealing a novel mechanism of DC functional diversification
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Kim, Jong-won. "Signalling initiation by blood dendritic cell antigen 2, a novel immunoglobulin receptor on plasmacytoid dendritic cells." Thesis, Imperial College London, 2018. http://hdl.handle.net/10044/1/63862.
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The focus of this project is a human-specific C-type lectin with potential roles in cell signalling: blood dendritic cell antigen 2 (BDCA-2). BDCA-2, a plasmacytoid dendritic cell-specific molecular marker, has been evaluated as a therapeutic target against auto-immune disorders, because antibodies to BDCA-2 inhibit the production of type I interferon. Accordingly, key goals of the project were to identify endogenous ligands for BDCA-2, to characterise the mechanism of ligand binding and ultimately to determine how ligands stimulate signalling pathways. A combination of BDCA-2 affinity chromatography column and mass spectrometry revealed that α2 macroglobulin and immunoglobulins, IgA, IgM and IgG are potential endogenous ligands in human serum. Competition binding studies conducted to characterise the binding affinity for each glycoprotein demonstrated that IgA has the highest affinity. Strategies for biochemical development of defined glycoforms of IgG Fc domain were established. The Chinese hamster ovary cell system for expression of Fc domain and the activity of enzymes necessary for chemoenzymatic glycoengineering have been tested. BDCA2 organisation in the cell membrane was studied by development of a transfected cell system which was analysed by affinity purification of BDCA-2 followed by analysis of protein-protein interactions. The results demonstrate that it is likely that BDCA-2 assembles with Fc receptor γ-chain in a 2:2 complex.
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Smits, Hermelijn Hélène. "Instruction of effector T cell programs by flexible dendritic cells." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2003. http://dare.uva.nl/document/86946.
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Mahmood, Sajid. "Diverse regulation of natural killer cell functions by dendritic cells." Public Library of Science, 2012. http://hdl.handle.net/1993/23963.
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Natural killer (NK) cells are innate lymphocytes with inherent ability to eliminate infected cells and produce several cytokines/chemokines. They express surface receptors to sense environment and interact with other immune cells including the Dendritic cells (DC). Reciprocally, DCs are also shown to activate NK-cells. NK/DC cross-talk is well-documented, yet the molecular interactions and the diverse NK-cell activities regulated by DC remain unclear.
Several target proteins such as MHC-1, Qa-1 mediate NK-cell target recognition. One such antigen, Ocil/Clr-b functions as a cognate ligand of NKR-P1B/D, NK-inhibitory receptor. In first aim of my study, I documented that deficiency of Ocil/Clr-b expression not only augmented the sensitivity of DC towards NK-cell cytotoxicity but also regulated the development of mature NK-cells. Thus suggesting NKR-P1B/D:Ocil to be another receptor:ligand system, besides Ly49:MHC-1, that regulates NK-cell responsiveness.
Src homology region 2-containing protein tyrosine phosphatase-1 (SHP-1) transmits inhibitory signals of the specific NK-inhibitory receptors, including NKRP-1B/D. SHP-1 silenced NK-cells showed unaffected target recognition towards prototypic target cells in this study. In addition, these cells also displayed an unexpected phenotype of self-killing in-vitro, thus implicated SHP-1 as an important regulator of some other unappreciated NK-cell functions.
The data from my third study suggest that DCs are directly implicated in the induction of NK-cell migration. In summary, using a novel live-cell imaging microfluidic platform and conventional transwell migration assay this project established a clear molecular link between DC-derived soluble factors such as IP-10 and NK cell-chemokine receptor such as CXCR3. Previously, GM-CSF was shown as an inflammatory cytokine, involved in the development of DC as well as in mediating Th-1 immune responses. In this study I found that GM-CSF regulates NK-cell migration negatively.
Lastly, the fourth aim of my thesis highlighted the critical role of immature-DC in the induction of maturation receptors (NK1.1 & Ly49) on differentiating NK-cells. I successfully established a multi-stage in-vitro NK-cell differentiation model and found that differentiating NK-cells required an active engagement with DCs, in addition to the soluble factors.
I believe my PhD project findings would impact the existing knowledge to harness DC-based NK cell therapies in clinical settings.October 2014
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Drakesmith, Alexander Hal. "Antigen processing and T cell priming by mouse dendritic cells." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300533.
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Stuart, Lynda Maria. "Cell death, dendritic cells and downregulation of the immune response." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/23214.
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Apoptotic cells are an important source of many autoantigens and the realization that dendritic cells (DCs), the main antigen presenting cell of the adaptive immune system, not only internalise such drying cells but present antigen derived from them had important implications for our understanding of autoimmunity, tumour immunology and anti-viral responses. The aim of this thesis was to explore the likely consequences of clearance of cells dying by constitutive apoptosis by myeloid phagocytes, with particular emphasis on the mechanism and outcome of DC clearance and the implications for autoimmunity. Firstly it will show that DCs generated from murine bone marrow demonstrated many characteristics attributed to DCs in vivo including endocytosis and phagocytosis and mature upon receipt of danger signals such as endotoxin. However, internalisation of apoptotic cells does not augment DC maturation but rather inhibits subsequent responses to LPS, rendering these DCs less efficient than their neighbours at stimulating naïve T cells. These effects do not appear to be due to secretion of inhibitory cytokines such as TGFβ or IL10 and are not dependent on CD36 or β3/5 integrins, receptors thought to be involved in DC internalisation of apoptotic cells. In addition apoptotic cells inhibit LPS driven IL12 production by ex vivo DCs and in mice immunised with apoptotic cells in vivo. Furthermore, macrophages, likely to be found in high numbers in the inflammatory site also inhibit DCs and these inhibitory effects could be further augmented by the presence of apoptotic cells. Taken together these data demonstrate that internalisation of apoptotic cells by myeloid phagocytes modulates the adaptive immune response and suggests that the likely outcome of internalisation of cells dying by constitutive apoptosis will be tolerance rather than autoimmunity.
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Kavikondala, Sushma. "Dendritic cell and B cell interactions in systemic lupus erythematosus." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39711523.
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Mann, Elizabeth R. "Tissue specific porperties of human dendritic cells and t-cells." Thesis, Imperial College London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.535005.
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Hornig, Julia. "Induction of gut homing T cells by systemic dendritic cells." Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/9011.
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An effective vaccine against mucosal pathogens such as the Human Immunodeficiency Virus 1 (HIV-1) must provide immunity at the mucosal level. Understanding the ability of mucosal dendritic cells (DCs) to induce gut homing lymphocytes plays a crucial parameter in the development of vaccines that mount a specific immune response in the intestine. Gut-tropic T cells are characterised by the expression of the integrin heterodimer α4β7 and the chemokine receptors CCR9 and CCR10, with CCR9 being specific for the small intestine. While CCR10 has been suggested to play a role in lymphocyte homing to the large intestine, together with CCR4, it has been implicated in lymphocyte trafficking to the skin. In addition, it is thought that induction of gut homing T cells is associated with the ability of intestinal DCs to metabolise vitamin A to retinoic acid (RA). Mucosal vaccination is known to induce mucosal and systemic immune responses, while systemic vaccination has been thought to only induce systemic immune responses. However, recent publications have shown systemic vaccination to induce mucosal immune responses. This project investigates the ability of different types of human systemic DCs to modulate expression of receptors specific to mucosal and skin homing T cells in the presence of retinoids and vitamin D. Co-culture of DCs with various T cell populations in the presence of RA revealed the ability of systemic DCs to increase α4β7 expression and decrease surface expression of cutaneous lymphocyte-associated antigen (CLA), a marker for skin homing T cells. We also showed that vitamin D plays a role in modulating CCR4 and CCR10 expression. Having investigated the ability of RA to modulate homing receptor expression on T cells, we confirmed the potential of systemic DCs to metabolize retinol and retinal in vitro by molecular means and flow cytometric analysis. Finally, we examined the role of retinoic acid receptors (RARs) in regulating α4β7 and CLA expressing T cells. This is the first study that investigates the potential of different subsets of human systemic DCs to differentially induce and modulate homing properties of T cells in vitro. The findings presented in this thesis could have major implications in the development of systemic vaccines aimed at inducing mucosal immune responses.
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Nie, Yingjie. "Defective dendritic cells and mesenchymal stromal cells in systemic lupus erythematosus and the potential of mesenchymal stromal cells as cell-therapy." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43278681.
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Peng, Judy Chun-Ju. "Optimization of Dendritic cells for cancer immunotherapy /." [St. Lucia, Qld.], 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18443.pdf.
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Salim, Sa'ad Yislam. "Mucosal dendritic cells in inflammatory bowel disease." Doctoral thesis, Linköpings universitet, Kirurgi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-52234.
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Crohn's disease, a chronic inflammation of the bowel, is a multi-factorial condition where uncontrolled immune responses to luminal bacteria occur in genetically predisposed individuals. The first observable clinical signs are small ulcers that form at a specialised form of epithelium, follicle-associated epithelium (FAB). The FAB covers immune inductive sites, Peyer's patches, which function primarily as sensory areas that sample the externaI gut environment. Dendritic cells are one of the key cells that are involved in sensing luminal contents and orchestrating the gut immune system. The main aim of this thesis was to determine whether the barrier of the FAB is breached in Crohn's disease and if dysfunctional immune regulators, namely dendritic cells, playaroIe in initiating and/or maintaining the chronic intestinal inflammation. Using biopsies and surgical specimens, we were able to show that in Crohn's disease, there was an increased transmucosaI transport of Escherichia coli compared to specimens from ulcerative colitis and non-inflammatory bowel disease (IBD) controIs. Dendritic cells internalised a higher percentage of bacteria that had translocated across the FAB in the Crohn's samples. Furthermore, significantly higher concentrations of TNF-u was released upon bacterial stimulation by tissues from patients with Crohn's disease than in controIs. We went on to characterise the dendritic cells present in the Peyer's patches of patients with Crohn's disease. We found an accumulation of both immature and mature dendritic cells beneath the FAB, in the sub-epithelial dome (SED). Normally, mature dendritic cells migrate towards T cell-rich areas. However, we observed mature dendritic cells accumulating in the SED because they lacked the CCR7 migratory receptor. Furthermore, they were more prone to take-up bacteria, and produced TNF-α. To study the function of mucosal dendritic cells, we performed isolation experiments and mixed Iymphocyte reactions. Dendritic cells from both the ileum and blood of patients with active Crohn's had reduced capacity for inducing T cell proliferation than non-IBD controIs. Blood dendritic cells of patients in remission had normalised function that was similar to dendritic cells from healthy controls. The SAMPl/YitFc mice, considered an appropriate murine model for Crohn's disease, had an inherent permeability defect that increased with the chronicity of intestinaI inflammation. However unlike in human Crohn's disease, dendritic cells did not seem to playaroIe in murine ileitis. This thesis highlights the accumulation of the actively surveying dendritic cells that are prone to bacterial internalisation, and points to their possible different functional roles in active versus in-active disease; thereby confirming dendritic cells as one ofthe key components in the pathogenesis ofCrohn's disease.
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Zangerle, Murray Tamsin Florencia Pamela. "Development of dendritic cells in the intestine." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7570/.
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The intestinal tract is exposed to a large variety of antigens such as food proteins, commensal bacteria and pathogens and contains one of the largest arms of the immune system. The intestinal immune system has to discriminate between harmless and harmful antigens, inducing tolerance to harmless antigens and active immunity towards pathogens and other harmful materials. Dendritic cells (DC) in the mucosal lamina propria (LP) are central to this process, as they sample bacteria from the local environment and constitutively migrate to the draining mesenteric lymph nodes (MLN), where they present antigen to naïve T cells in order to direct an appropriate immune response. Despite their crucial role, understanding the function and phenotype of LP DC has been hampered by the fact that they share phenotypic markers with macrophages (mφ), which are the dominant population of mononuclear phagocyte (MP) in the LP. Recent work in our own and other laboratories has established gating strategies and phenotyping panels that allow precise discrimination between intestinal DC and mφ using the mφ specific markers CD64 and F4/80. In this way four bona fide DC subsets with distinct functions have been identified in adult LP based on their expression of CD11b and CD103 and a major aim of my project was to understand how these subsets might develop in the neonatal intestine. At the beginning of my PhD, the laboratory had used these new methods to show that signal regulatory protein α (SIRPα), an inhibitory receptor expressed by myeloid cells, was expressed by mφ and most DC in the intestine, except for those expressing CD103 alone. In addition, mice carrying a non-signalling mutation in SIRPα (SIRPα mt) had a selective reduction in CD103+CD11b+ DC, a subset which is unique to the intestinal LP. This was the basis for the initial experiments of my project, described in Chapter 3, where I investigated if the phenotype in SIRPα mt mice was intrinsic to haematopoietic cells or not. To explore this, I generated bone marrow (BM) chimeric mice by reconstituting irradiated WT mice with SIRPα mt BM, or SIRPα mt animals with WT BM. These experiments suggested that the defect in CD103+CD11b+ DC was not replicated in DC derived from BM of SIRPα origin. However as this seemed inconsistent with other data, I considered the possibility that 18 the phenotype may have been lost with age, as the BM chimeric mice were considerably older than those used in the original studies of SIRPα function. However a comparison of DC subsets in the intestine of WT and SIRPα mt mice as they aged provided no conclusive evidence to support this idea. As these experiments did show age-dependent effects on DC subsets, in Chapter 4, I went on to investigate how the DC populations appeared in the intestine and other tissues in the neonatal period. These experiments showed there were few CD103+CD11b+ DC present in the LP and migratory DC compartment of the MLN in the neonate and that as this population gradually increased in proportion with age, there was a reciprocal decrease in the relative proportion of CD103-CD11b+ DC. Interestingly, most of the changes in DC numbers in the intestine were found during the second or third week of life when the weaning process began. To validate my findings that there were few CD103+CD11b+ DC in the neonate and that this was not merely an absence of CD103 upregulation, I examined the expression of CD101 and Trem-1, markers that other work in the laboratory had suggested were specific to the CD103+CD11b+ DC lineage. My work showed that CD101 and Trem-1 were co- expressed by most CD103+CD11b+ DC in small intestine (SI) LP, as well as a small subset of CD103-CD11b+ DC in this tissue. Interestingly, Trem-1 was highly specific to the SI LP and migratory DC in the MLN, but absent from the colon and other tissues. CD101 expression was also only found on CD11b+ DC, but showed a less restricted pattern of distribution, being found in several tissues as well as the SI LP. The relative timing of their development suggested there might be a relationship between CD103+CD11b+ and CD103-CD11b+ DC and this was supported by microarray analysis. I hypothesised that the CD103-CD11b+ DC that co-expressed CD101 and Trem-1 may be the cells that developed into CD103+CD11b+ DC. To investigate this I analysed how CD101 and Trem-1 expression changed with age amongst the DC subsets in SI LP, colonic LP (CLP) and MLN. The proportion of CD101+Trem-1+ cells increased amongst CD103+CD11b+ DC in the SI LP and MLN with age, while amongst CD103+CD11b+ DC in the CLP this decreased. This was not the same in CD103-CD11b+ DC, where CD101 and Trem-1 expression was more varied with age in all tissues. CD101 and Trem-1 were not expressed to any great extent on CD103+CD11b- or CD103-CD11b- DC. The phenotypic development of the 19 intestinal DC subsets was paralleled by the gradual upregulation of CD103 expression, while the production of retinoic acid (RA), as assessed by the AldefluorTM assay, was low early in life and did not attain adult levels until after weaning. Thus DC in the neonatal intestine take some time to acquire the adult pattern of phenotypic subsets and are functionally immature compared with their adult counterparts. In Chapter 5, I used CD101 and Trem-1 to explore the ontogeny of intestinal DC subsets in CCR2-/- and SIRPα mt mice, both of which have selective defects in one particular group of DC. The selective defect seen amongst CD103+CD11b+ DC in adult SIRPα mt mice was more profound in mice at D7 and D14 of age, indicating that it may be intrinsic to this population and not highly dependent on environmental factors that change after birth. The expression of CD101 and Trem-1 by both CD103+CD11b+ and CD103-CD11b+ DC was reduced in SIRPα mt mice, again indicating that this entire lineage was affected by the lack of SIRPα signalling. However there was also a generalised defect in the numbers of all DC subsets in many tissues from early in life, suggesting there was compromised development, recruitment or survival of DC in the absence of SIRPα signalling. In contrast to the findings in SIRPα mt mice, more CD103+CD11b+ DC co-expressed CD101 and Trem-1 in CCR2-/- mice, while there were no differences in the expression of these molecules amongst CD103-CD11b+ DC. This may suggest that CCR2+ CD103-CD11b+ DC are not the cells that express CD101 and Trem-1 that are predicted to be the direct precursors of CD103+CD11b+ DC. I also examined the expression of DC growth factor receptors on DC subsets from mice of different ages, but no clear age or subset- related patterns of the expression of mRNA for Csf2ra, Irf4, Tgfbr1 and Rara could be observed. Next, I investigated whether Trem-1 played any role in DC development. Preliminary experiments in Trem-1-/- mice show no differences between any of the DC subsets, nor were there any selective effects on individual subsets when DC development from Trem-1-/- KO and WT BM was compared in competitive chimeras. However these experiments were difficult to interpret due to viability problems and because I found an unexpected defect in the ability of Trem-1-/- BM to generate all DC, irrespective of whether they expressed Trem-1 or not. 20 The final experiments I carried out were to examine the role of the microbiota in driving the differentiation of intestinal DC subsets, based on the hypothesis that this could be one of the environmental factors that might influence events in the developing intestine. To this end I performed experiments in both antibiotic treated and germ free adult mice, both of which showed no significant phenotypic differences amongst any of the DC subsets. However the study of germ free mice was compromised by recent contamination of the colony and may not be the conclusive answer. Together the data in this thesis have shown that the population of CD103+CD11b+ DC, which is unique to the intestine, is not present at birth. These cells gradually increase in frequency over time and as this occurs there is a reciprocal decrease in the frequency of CD103-CD11b+ DC. Along with other results, this leads to the idea that there may be a linear developmental pathway from CD103-CD11b+ DC to CD103+CD11b+ DC that is driven by non-microbial factors that are located preferentially in the small intestine. My project indicates that markers such as CD101 and Trem-1 may assist the dissection of this process and highlights the importance of the neonatal period for these events.
25
Major, James R. "Interactions of dendritic cells with vaccinia virus." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401096.
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Paterson, Alison M. "Tolerance induction by cytokine-modulated dendritic cells." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424869.
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Edwards, Alexander Daniel. "Recognition of microbial patterns by dendritic cells." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407107.
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Soares, Sandra Clara Chaves. "Interactions between dendritic cells and Mycobacterium tuberculosis." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367559.
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Macdougal, Thomas Hugh James. "Interactions between dendritic cells and HIV-1." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392283.
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Scott, Charlotte Louise. "Characterisation of dendritic cells in the intestine." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/4829/.
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Due to the large surface area of the gut and its continual exposure to a wide variety of agents including dietary constituents, commensal bacteria and pathogens, the intestinal arm of the immune system has evolved to be the largest component of the immune system. It must be able to discriminate between harmless and harmful antigens, so that it can induce tolerance to harmless commensal, self or dietary antigens, but active immunity against pathogens. As the sentinels of the immune system, intestinal dendritic cells (DCs) are central to these processes, continually sampling antigen in the environment and migrating to the mesenteric lymph nodes (MLNs), where they present the antigen to naïve T cells and induce appropriate T cell responses. However the nature and functions of DCs in the intestine remains a topic of debate. Their characterisation has been hampered by the use of non-specific and overlapping markers which has led to intestinal DCs being confused with other cells of the mononuclear phagocyte system, especially macrophages (mφs) which vastly outnumber DCs in the intestinal mucosa. While considerable progress has been made in recent years with the identification of CD103 and CX3CR1 as mutually exclusive markers of DCs and mφs respectively, it has become assumed that CD103+ DCs are intrinsically tolerogenic and thus it remains unclear how DCs contribute to active immunity in the intestine. Furthermore it is unknown whether CD103 is sufficient to define all intestinal DCs, or whether bona fide CD103- DCs may also exist. Thus a major aim of my project was to develop methods that allowed precise characterisation of the mononuclear phagocytes in the intestinal lamina propria (LP) and examine the functions of phenotypically defined subsets. As part of this, I also examined the contribution of the inhibitory signalling receptor, signal regulatory protein alpha (SIRPα) co-expressed by CD11b+ DCs, in regulating intestinal DC function. In Chapter 3, I set out to examine the phenotype of mononuclear phagocytes in the small intestine lamina propria (SI LP). Initially I confirmed previous studies that CD103 and CX3CR1 were mutually exclusive markers of DCs and mφs respectively. This identified 2 populations of DCs separated on the basis of CD11b expression, together with two populations of mφs distinguished by their levels of CX3CR1. However, further experiments examining F4/80 expression in combination with the recently identified mφ-specific marker CD64 showed that the CX3CR1int CD103- MPs were heterogeneous. Although the majority were F4/80+CD64+CD11b+ mφs, I could also identify two additional populations that were F4/80-CD64- and could be separated on the basis of CD11b expression. I hypothesised these were DCs and this was supported by the fact that all 4 subsets of putative DCs could also be found amongst CD11c+MHCIIhi migratory DCs in the MLNs and in pseudo-afferent intestinal lymph. All the subsets also expressed genes and markers of DCs but not mφ and were dependent on Flt3L in vivo. Unlike CD64+ mφs, the DC subsets had no ability to phagocytose E. coli particles. Four similar subsets were also identified in the colonic LP, however the proportions of the subsets in this location were distinct from those seen in the SI LP. While the CD103+CD11b+ DCs were the main subset in the SI LP, in the colonic LP the CD103+CD11b- DCs dominated. Having identified two novel populations of genuine CD103- DCs in the intestinal LP, in Chapter 4 I went on to examine their origin. Previous reports had shown that CD103+ LP DCs were derived from DC-committed precursors (pre-DCs), whereas CD103- MPs were reported to be of monocyte origin. However as I had shown the CD103- MPs to include both DCs and mφs, it was necessary to re-examine their origin using appropriate gating strategies. Adoptive transfer of pre-DCs from the BM into resting WT mice generated all subsets of DCs in the LP, including the two novel populations of CD103- DCs I had identified. In contrast adoptive transfer of Ly6Chi monocytes into monocytopenic CCR2-/- recipients generated mφs exclusively. By comparing the small intestine, colon and spleen, I could show that the development of pre-DCs was determined by the tissue they entered, as the progeny took on the same subset profiles as seen in the endogenous DC populations. Thus the differentiation of pre-DCs appears to be driven by the local microenvironment. By tracking the appearance of donor-derived DCs over time, I could monitor their differentiation in situ. These studies and experiments using BrdU incorporation showed that all DC subsets turned over much more rapidly in vivo than mφs and that a significant proportion were actively dividing in situ. No clear differences suggesting a precursor-product relationship between any of the DC subsets could be seen in these kinetic experiments. To gain a better idea of how the DC subsets might develop, I also examined them in neonatal animals and examined the effects of administering broad-spectrum antibiotics. These studies demonstrated that the CD103+CD11b+ DCs were likely regulated by the presence of specific microbiota as they did not develop in the neonatal animals until day 7 after birth and were increased in proportion following administration of antibiotics. In Chapter 5, I examined how the DC populations might behave during inflammation, using DSS colitis, post-operative ileus and infection with Citrobacter rodentium as models. DSS-colitis caused considerable inflammatory infiltrate and the number of DCs was increased, however there were no subset specific differences. Post-operative ileus also caused inflammation characterised by monocyte and neutrophil infiltration, but had few effects on the DC populations. Infection with C. rodentium resulted in a selective increase in the number of CD103- DCs in the colonic LP, suggesting these may be involved in modulating the Th17 response which characterises the protective immune response in this infection. By transferring pre-DCs into colitic mice, I found that these still gave rise to all the DC subsets during inflammation. In Chapter 6, I examined the functions of the phenotypically defined subsets of LP DCs by pulsing them with ovalbumin (OVA) protein in vitro and culturing them with OVA-specific CD4+ or CD8+ T cells. Consistent with their expression of CD8α and XCR1, I found the CD103+CD11b- DCs to be the most efficient at cross-presenting antigen to naïve CD8+ T cells and they were also the most efficient inducers of IFNγ-producing CD4+ T cells. All populations of DCs could induce FoxP3+ TReg cells, but consistent with their ability to produce retinoic acid as measured by the ALDEFLUOR assay, the CD103+ DC subsets were most efficient at this. The CD103+CD11b- subset also expressed the TGFβ-activating integrin αvβ8. In contrast, induction of IL17a-producing CD4+ T cells was a function of CD103+CD11b+ and CD103-CD11b+ DCs, with the latter being the most efficient. In Chapters 7 and 8, I examined the role of the inhibitory molecule SIRPα in intestinal DC behaviour by examining the DC populations in SIRPα mutant (mt) mice, which have a truncated cytoplasmic domain and hence cannot signal intracellularly. Despite being expressed by most myeloid cells including all CD11b+ DC subsets and CD64+ mφs, SIRPα mt mice had a selective defect in the number of CD103+CD11b+ DCs in the LP and MLN. This correlated with a reduction in the number of Th17 cells in the LP of steady state SIRPα mt mice and these mice showed reduced levels of Th17 cell induction after antigen-specific immunisation and infection by C. rodentium. In parallel, SIRPα mt mice had impaired clearance of C. rodentium infection. T cells from SIRPα mt mice did not have an intrinsic defect in their ability to be polarised to the Th17 phenotype and CD103+CD11b+ DCs from SIRPα mt LP were fully capable of priming Th17 cells in vitro.
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Eaton, Laura. "Skin dendritic cells : activation, maturation and migration." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/skin-dendritic-cells-activation-maturation-and-migration(0831ed5e-c580-406c-a404-4b1eb59b040d).html.
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Langerhans’ cells (LC) are the dendritic cells (DC) of the epidermis and, as sentinels of the immune system, act as a bridge between the innate and adaptive immune responses. When LC, and other DC, recognise an antigen or pathogen they mature and are stimulated to migrate to the lymph nodes, where they orchestrate immune responses. Pathogen derived toll-like receptor (TLR) ligands, and chemical allergens, are recognised as being potentially harmful and stimulate LC to mobilise and mature. Cytokine signals, including tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-18, all induce LC migration and are required for initiating LC mobilisation in response to certain contact allergens. Subsequently, chemokines promote the migration and localisation of LC within the draining lymph nodes. Chemokines are also involved in shaping the adaptive immune response by promoting differential T cell activation, such as T helper (Th)1 or Th2 responses, which are involved in immunity against different pathogens, and also in the development of different types of chemical allergy. The hypothesis is that LC phenotype (activation, migration and chemokine production), is dependent on the nature of the challenge ligand. The murine LC-like cell line XS106 was used to investigate the response of LC following stimulation with TLR ligands and chemical allergens. In addition, LC migration in response to these stimuli was investigated in vivo and the role of TNF-α was examined using mice deficient in either one of the two TNF-α receptors; TNF-R1 or TNF-R2.XS106 cells and freshly isolated LC were associated with a selective type 2 immune response, as determined by preferential expression of type 2 associated chemokines. Furthermore, XS106 cells responded to type 2, but not to type 1, associated TLR ligands. In contrast, all of the TLR ligands tested induced the migration of LC from the epidermis in vivo. Similarly, chemical allergens failed to induce a maximal response of XS106 cells, but did induce the migration of LC in vivo. There were differences in LC migration between the two mouse strains tested, with C57/BL6 strain mice being less responsive to administration of TNF-α and the contact allergen oxazolone compared with BALB/c strain mice. However, C57/BL6 and BALB/c strain mice responded similarly after exposure to the contact allergen 2,4-dinitrochlorobenzene (DNCB). Furthermore, DNCB was able to induce LC migration in mice deficient in TNF-R2, the TNF-α receptor expressed by LC.Collectively, these data suggest a paradigm in which keratinocytes and LC in the epidermis have distinct roles in promoting type 1 and type 2 immune responses, respectively. Therefore, LC may not be activated directly by certain TLR ligands or chemical allergens that are associated with type 1 responses. Consequently the migration of LC in vivo after encounter with these stimuli may be secondary to interaction with keratinocytes, or with other skin resident cells. Together, LC and keratinocytes allow the epidermis to respond to a range of pathogens, in addition to developing the necessary type 1 and type 2 responses. Chemical allergens may have divergent cytokine signalling requirements for the induction of LC migration as, unlike other contact allergens (and other stimuli such as irritant and ultraviolet [UV]B exposure), DNCB may induce LC migration independently of TNF-α.
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Wildenberg, Manon Elisabeth. "Monocytes and dendritic cells in Sjögren's syndrome." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/12619.
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Pinzon-Charry, Alberto. "Characterisation of blood dendritic cells in patients with cancer /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18933.pdf.
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Raïch, Regué Dàlia. "Generation of Tolerogenic Dendritic Cells for Cell Therapy in Multiple Sclerosis." Doctoral thesis, Universitat Autònoma de Barcelona, 2012. http://hdl.handle.net/10803/96710.
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L’esclerosi múltiple (EM) és considerada una malaltia autoimmune crònica que afecta el sistema nerviós central. Els tractaments actuals pels pacients amb EM remitent-recurrent (EM-RR) redueixen la freqüència dels brots i l’activitat inflamatòria general, però el seu efecte en la progressió de la malaltia encara no està clar. Per això és necessari desenvolupar noves aproximacions terapèutiques més específiques per tal de modificar el curs de la malaltia. En aquest sentit, una estratègia terapèutica interessant és la inhibició o supressió específica de les cèl·lules T autoreactives amb la finalitat de restablir la tolerància en malalties autoimmunitàries com l’EM.
L’objectiu principal d’aquest treball ha estat la generació i caracterització de cèl·lules dendrítiques tolerogèniques (tolDCs) de pacients amb EM-RR, carregades amb pèptids de la mielina, com a eina terapèutica per restablir la tolerància als antígens de la mielina en aquests pacients.
Els resultats obtinguts mostren que la utilització de diferents agents immunosupressors i estímuls de maduració permet generar tolDCs de grau clínic amb diferències rellevants per a la seva aplicació terapèutica. S’ha valorat la viabilitat, el fenotip, el perfil de les citocines produïdes, l’estabilitat i la funcionalitat d’aquestes tolDCs. La comparació de diferents agents tolerogènics de grau clínic (dexametasona, rapamicina i vitamina-D3) ha permès observar que les tolDCs tractades amb dexametasona mostren un fenotip semi-madur i produeixen grans quantitats de IL-10; que les tolDCs tractades amb rapamicina redueixen la secreció d’interferó-γ dels limfòcits T co-cultivats i expandeixen cèl·lules T reguladores; i finalment que les tolDCs obtingudes amb vitamina-D3 presenten un fenotip semi-madur, produeixen IL-10, i disminueixen la producció d’interferó-γ dels limfòcits T. Aquestes característiques, juntament amb la reproductibilitat dels resultats en les diferents mostres, fan que la vitamina-D3 hagi estat considerat l’agent més adient per generar tolDCs com a eina terapèutica per a l’EM. Tenint en compte l’estímul de maduració, el còctel de citocines pro-inflamatòries −composat per TNF-α, IL-1β i PGE-2− és considerat com a estímul maduratiu òptim per a la generació de tolDCs (obtingudes amb vitamina-D3), ja que aquestes tolDCs han estat les úniques en mostrar una estabilitat funcional i una capacitat de suprimir la resposta immunitària in vitro.
La generació de tolDCs de pacients amb EM-RR (generades amb vitamina-D3 i madurades amb el còctel de citocines pro-inflamatòries) no ha mostrat diferències significatives en comparació amb tolDCs obtingudes de controls sans, ambdues presentant un perfil tolerogenic. Les tolDCs de pacients amb EM-RR carregades amb pèptids de la mielina són capaces d’induir un estat d’hipo-resposta/anergia, estable i antigen-específica, als limfòcits T autòlegs i reactius a la mielina in vitro.
En resum, aquest treball ha conduit al desenvolupament d’un protocol per generar tolDCs de grau clínic i ha establert les bases per al seu ús com a eina terapèutica amb la finalitat de restablir la tolerància en pacients amb EM-RR.Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Current treatments for relapsing-remitting multiple sclerosis (RR-MS) patients decrease the frequency of relapses and reduce inflammatory activity in a nonspecific manner, but their effect on disease progression is still unclear. Therefore, in order to modify the course of MS, new and more specific therapeutic approaches are necessary. Specific inhibition or deletion of autoreactive T cells represents an interesting goal for restoring peripheral tolerance in autoimmune diseases such as MS. The main goal of this work has been to generate and characterize tolerogenic dendritic cells (tolDCs) from RR-MS patients, loaded with myelin peptides as specific antigen, as a therapeutic tool to re-establish tolerance to myelin-antigens in these patients. Our results show that using different immunosuppressive drugs and different maturation stimulus led to the generation of clinical-grade tolDCs products with differences that are relevant to therapeutic applicability. We evaluated the viability, phenotype, cytokine profile, stability and functionality of these tolDCs. The comparison of different pharmacological grade tolerogenic agents (dexamethasone, rapamycin and vitamin-D3) led to the observation that dexamethasone-treated DCs showed a semi-mature phenotype and high IL-10 secretion; that rapamycin-treated DCs impaired IFN-γ in co-cultured T cells and expanded T regulatory cells; and finally that vitamin-D3-treated DCs presented a semi-mature phenotype, produced IL-10, and reduced IFN-γ in T cells. These features, along with their reproducibility among different samples, made consider vitamin-D3 as the most convenient of the three compared agents to generate tolDCs for MS therapy. Regarding the maturation of tolDCs, the cytokine cocktail (composed by TNF-α, IL-1β and PGE-2) was determined as the optimal maturation stimulus to generate tolDCs (induced by vitamin-D3 treatment), since these tolDCs were the unique exhibiting functional stability and capability to suppress an immune response in vitro. The generation and characterization of tolDCs from RR-MS patients (generated with vitD3 and maturated with the pro-inflammatory cytokine cocktail), showed no significant differences compared with tolDCs generated from healthy controls, both presenting a tolerogenic profile. Importantly, myelin peptide-loaded tolDCs from RR-MS patients induced antigen-specific and stable hyporesponsiveness in autologous myelin-reactive T cells in vitro. Altogether this work has conducted to the development of a protocol to generate clinical-grade tolDCs and set up the bases for their use as a therapeutic tool to re-establish tolerance in RR-MS patients.
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Barroso, Herrera Osquel Miguel. "Manipulation of antigen-specific T cell responses by modified dendritic cells." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405941.
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Worsley, Alan G. F. "T-cell polarisation by dendritic cells : a role for Notch ligands?" Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/3281.
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The intention of the work described in this thesis was to identify whether the Notch signalling pathway is utilized by antigen presenting cells in order to influence CD4+ adaptive immune responses. The notion that Notch proteins may be involved in polarising CD4+ T cells is relatively recent and most of the work that had been done in this area so far has concentrated on the consequences of Notch signalling within T cells. In contrast, the work that I have done has focussed on Notch ligand expression by antigen presenting cells and addresses the question whether Notch signalling is a redundant, necessary or irrelevant tool in the arsenal of antigen presentation.
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Williams, Charlotte Anne. "The immunoregulatory role of dendritic cells in response to cell deaths." Thesis, University of the West of England, Bristol, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444498.
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Walwyn-Brown, Katherine. "Control of Th2 polarisation by dendritic cells and natural killer cells." Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/control-of-th2-polarisation-by-dendritic-cells-and-natural-killer-cells(fd15f834-f926-40f1-88ff-217bf1fbf263).html.
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Type 2 (Th2) immune responses are required for immune defence against helminths, but can also have pathogenic effects in allergic conditions. This thesis examined two factors which may influence Th2 immunity at a cellular and molecular level: cross-talk between Natural Killer (NK) cells and dendritic cells (DCs) and the cell surface organisation of DCs. Cross-talk between NK cells and DCs is well-established to impact Th1 responses against tumours and infection; however the influence of this interaction during Th2 inflammation is unknown. To investigate this, human monocyte-derived DCs were stimulated in vitro with different pathogen-associated molecules; LPS or Poly(I:C) which polarise a Th1 response, or soluble egg antigen (SEA) from the helminth worm Schistosoma mansoni, a potent Th2-inducing antigen. These cells were then combined with autologous NK cells. Confocal microscopy showed polarisation of the NK cell microtubule organising centre (MTOC) and accumulation of LFA-1 at contacts between NK cells and immature or Th2-polarising DCs, but not Th1-polarising DCs, indicative of the assembly of an activating immune synapse. NK cells did not lyse DCs treated with LPS or Poly(I:C), but degranulated to and lysed both immature DCs and Th2 polarising DCs. Antibody blockade of NK cell activating receptors NKp30 and DNAM-1 prevented this lysis. Furthermore, depletion of NK cells in mice which were then transferred with Th2 polarising DCs led to an enhanced Th2 recall response. Thus, these data indicate a previously unrecognised role of NK cell cytotoxicity in restricting the pool of DCs involved in Th2 immune responses. Secondly, this thesis investigated the nanoscale organisation of MHC-II on the surface of Th1 and Th2 polarising DCs using ground state depletion super-resolution microscopy. MHC-II was relatively homogenously distributed across the membrane with no significant changes in clustering between immature, Th1 and Th2 polarising DCs. In contrast, imaging CD74, which can mediate internalisation of MHC-II, revealed increased expression and a more homogenous distribution of this receptor on the surface of Th2-polarising DCs compared to Th1-polarising DCs. These data suggest that changes in the clustering of CD74 could modulate MHC-II surface expression during Th2 responses. Overall, the results in this thesis indicate that both molecular and cellular level modulation of DC function contribute to the development of Th2 responses.
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Miller, Jonathan. "Modulation of dendritic cells and autoimmunity by apoptotic and necrotic cells." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-dendritic-cells-and-autoimmunity-by-apoptotic-and-necrotic-cells(eab00223-e5a2-4fdd-8baf-aa5966c87ede).html.
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As the principal antigen-presenting cells to T cells, dendritic cells (DCs) have a key role in the balance of immunity and autoimmunity. They are essential in two major, converse roles - eliciting T cell immune responses to pathogenic material, and maintaining peripheral tolerance to self-tissue by inhibiting self-reactive T cells. These functions involve the processing of pathogenic or self antigens and subsequent presentation of antigenic peptides on MHC to antigen-specific T cells. DC recognition of conserved pathogenic markers induces a mature phenotype that governs immunogenic presentation to T cells and, consequently, the adaptive immune response. In contrast, DC recognition of self tissue suppresses maturation, instead inducing a tolerogenic phenotype that induces self antigen-specific T cell to die, become anergised, or converted to T regulatory cells. Apoptotic cells are the major source of self-antigen for the maintenance of peripheral tolerance, and their defective clearance by DCs is implicated in autoimmunity. Apoptotic cells are thought to actively suppress maturation of DCs and inhibit the possible immune responses promoted by proinflammatory mediators released from necrotic cells. However, the immune function of apoptotic cells and their relative influence over necrotic cells are highly contested, partially due to the complex nature of immunogenicity arising from the sourcing and generation of apoptotic cells. In this investigation, various methods of inducing apoptosis and necrosis are evaluated. Definitive methods of inducing well-characterised cell death are then employed to compare the effects of apoptotic and necrotic cells on dendritic cells and in vitro and in vivo immune responses. Reported here are in vitro findings that support previous reports of the anti-inflammatory response of DCs to apoptotic cells, and the inflammatory response of DCs to necrotic cells. The previously-reported inhibitory effect of apoptotic cells on LPS-induced secretion of Th1 cytokines is supported here, but the inhibitory effect of apoptotic cells on LPS-induced upregulation of co-stimulatory molecules is contested. Novel findings describe the upregulation of DC expression of co-inhibitory molecules induced by both apoptotic cells and necrotic cells. Apoptotic cells, but not necrotic cells, had a suppressive effect on CpG-induced upregulation of co-stimulatory molecules and pro-inflammatory cytokines. Apoptotic cells suppressed the capacity of untreated and CpG-treated, but not LPS-treated, DCs to elicit IFNγ production by T cells. Apoptotic cells, but not necrotic cells, induced regulatory T cells and partially restored their CpG-suppressed induction. Finally, apoptotic cell-modulation of DCs inhibited the induction of autoimmunity in a novel modification of an in vivo model of diabetes. Interestingly, novel evidence for the possibility of necrotic cell-induced tolerance by means of direct T cell killing is addressed.
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Izquierdo-Useros, Nuria. "Maturation of Dendritic Cells & HIV Transmission to CD4(+) T cells." Doctoral thesis, Universitat Autònoma de Barcelona, 2009. http://hdl.handle.net/10803/3822.
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Las células dendríticas (DCs) están especializadas en la presentación de antígeno. Sin embargo, las DCs expuestas al virus de la inmunodeficiencia humana (VIH) también son capaces de transmitir una potente infección citopática a los linfocitos T CD4+, un proceso que frecuentemente se ha relacionado con la capacidad que tiene el receptor DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) para unirse de forma específica a la glicoproteína de la envuelta viral. La maduración de las DCs puede aumentar la eficiencia de transmisión del VIH a los linfocitos T CD4+ a través de la trans-infección. Nuestro objetivo en este trabajo ha sido comparar el efecto de la maduración en las células dendríticas derivadas de monocitos (MDDCs) y en las células dendríticas mieloides derivadas de sangre durante el proceso de captura del VIH. Para analizar la captura y transmisión viral a las células diana competentes in vitro de un VIH pseudotipado con envuelta y el virus homólogo replicativo utilizamos las técnicas de detección de p24gag, actividad luciferasa y microscopía electrónica y confocal. Así, observamos que la maduración de las MDDCs o las DCs mieloides aumenta la captura activa del VIH de una forma independiente del receptor DC-SIGN o de la glicoproteína de la envuelta viral, incrementándose también el tiempo de retención del virus capturado. Además, verificamos que la mayor transmisión viral de las DCs maduras (mDCs) a los linfocitos T CD4+ es altamente dependiente de una captura viral activa, un proceso endocítico mediado a través de dominios de membrana enriquecidos en colesterol. Notablemente, mientras que las mDCs concentran el virus capturado en una única vesícula positiva para las tetraspaninas CD63 y CD81, las DCs inmaduras carecen de dichas estructuras, lo que sugiere un proceso de tráfico intracelular viral diferencial en cada tipo celular.
Los exosomas son vesículas celulares secretadas que pueden ser internalizadas por las DCs, contribuyendo a la activación específica de antígeno de los linfocitos naive T CD4+. En esta tesis demostramos que el VIH puede explotar esta ruta intrínseca a las mDCs que permite la diseminación de antígenos a través de los exosomas, permitiendo así la trans-infección de los linfocitos T CD4+. Tras la maduración de las DCs, la captura del VIH-1, las partículas pseudovirales VIH-1 Gag-eGFP (VLPs) y los exosomas aumenta significativamente, acumulándose dentro de un compartimento CD81+. La captura de estas partículas se inhibió preincubando las mDCs con las VLPs o los exosomas, lo que sugiere que la expresión de determinantes moleculares comunes en la superficie de las VLPs y los exosomas es necesaria para la internalización mediada por las mDCs. Así mismo, la captura mediada por las mDCs es insensible a un tratamiento proteolítico, pero puede bloquearse cuando los virus, las VLPs o los exosomas se producen en células tratadas con inhibidores de la biosíntesis de los esfingolípidos, que alteran la composición lipídica de las partículas que emergen.
Por último, las VLPs y los exosomas capturados por las mDCs se transmiten a los linfocitos T CD4+ de una forma independiente de la glicoproteína de la envuelta viral, resaltando la existencia de una nueva ruta de diseminación viral.
En general, estas observaciones ayudan a explicar la mayor capacidad de las mDCs para transmitir el VIH a los linfocitos T CD4+, un proceso que potencialmente puede contribuir a la diseminación viral en los nódulos linfáticos in vivo, donde la replicación viral tiene lugar de forma mayoritaria y hay una interacción continua entre las células T CD4+ susceptibles y las mDCs.
Dendritic cells (DCs) are specialized antigen-presenting cells. However, DCs exposed to human immunodeficiency virus (HIV) are also able to transmit a vigorous cytopathic infection to CD4+ T lymphocytes, a process that has been frequently related to the ability of DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) to bind HIV-1 envelope glycoproteins. Maturation of DCs can increase the efficiency of HIV transmission through trans-infection. We aimed to comparatively study the effect of maturation in monocyte derived dendritic cells (MDDCs) and blood-derived myeloid DCs during HIV capture process. In vitro capture and transmission of envelope pseudotyped HIV-1 and its homologous replication competent virus to susceptible target cells was assessed by p24gag detection, luciferase activity, and both confocal and electron microscopy. Maturation of MDDCs or myeloid DCs enhanced active capture of HIV in a DC-SIGN and viral envelope glycoprotein independent manner, increasing the lifespan of trapped virus. Moreover, higher viral transmission of mature DCs (mDCs) to CD4+ T lymphocytes was highly dependent on active viral capture, a process mediated through cholesterol-enriched domains. Mature DCs concentrated captured virus in a single large vesicle staining for CD81 and CD63 tetraspanins, while immature DCs lacked these structures, suggesting different intracellular trafficking processes.
Exosomes are secreted cellular vesicles that can be internalized by DCs contributing to antigen specific naive CD4+ T lymphocyte activation. Here, we demonstrate that HIV can exploit this exosome antigen-dissemination pathway intrinsic to mDCs for mediating trans-infection of CD4+ T lymphocytes. Capture of HIV-1, HIV-1 Gag-eGFP viral like particles (VLPs) and exosomes by DCs was upregulated upon maturation, resulting in localization within a CD81+ compartment. Uptake of VLPs or exosomes could be inhibited by a challenge with either particle, suggesting that the expression of common determinant(s) on VLP or exosome surface is necessary for internalization by mDCs. Capture by mDCs was insensitive to proteolysis, but blocked when virus, VLPs, or exosomes were produced from cells treated with sphingolipid biosynthesis inhibitors that modulate the lipid composition of the budding particles. Finally, VLPs and exosomes captured by mDCs were transmitted to CD4+ T lymphocytes in an envelope glycoprotein-independent manner, underscoring a new potential viral dissemination pathway.
Overall, these observations help explaining the greater ability of mDCs transferring HIV to CD4+ T lymphocytes, a process that can potentially contribute to the viral dissemination at lymph nodes in vivo, where viral replication takes place and there is a continuous interaction between susceptible T-cells and mDCs.
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Wehner, Rebekka, Kristin Dietze, Michael Bachmann, and Marc Schmitz. "The Bidirectional Crosstalk between Human Dendritic Cells and Natural Killer Cells." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-137394.
Full textAbstract:
Dendritic cells (DCs) are professional antigen-presenting cells, which display an extraordinary capacity to induce T-cell responses. Recent findings revealed that DCs also play a crucial role in the activation of natural killer (NK) cells representing important effectors in the innate immune defense against viruses and tumors. Here, we summarize various studies investigating the bidirectional crosstalk between human DCs and NK cells. In this context, it has been reported that DCs efficiently enhance CD69 expression, proliferation, interferon (IFN)-γ secretion and cytotoxic activity of NK cells. Cell membrane-associated molecules as well as soluble factors such as interleukin-12, tumor necrosis factor-α and type I IFNs contributed to DC-mediated NK cell activation. Reciprocally, the ability of human NK cells to enhance the immunostimulatory capacity of DCs was shown. Thus, NK cells promoted the maturation of DCs and markedly augmented their capacity to produce proinflammatory cytokines and to stimulate T-cell responses. The NK cell-mediated effects on DCs were dependent on cell membrane-associated molecules such as NKp30 and soluble factors such as tumor necrosis factor-α and IFN-γ. In conclusion, the reciprocal activating interaction between human DCs and NK cells may play a pivotal role in the immune defense against viruses and tumorsDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Raveney, Ben J. E. "Interactions between CD8+ T cells and bone marrow-derived dendritic cells." Thesis, University of Bristol, 2006. http://hdl.handle.net/1983/dbbc656f-a103-4787-aeb9-f203c3f0082b.
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Wehner, Rebekka, Kristin Dietze, Michael Bachmann, and Marc Schmitz. "The Bidirectional Crosstalk between Human Dendritic Cells and Natural Killer Cells." Karger, 2011. https://tud.qucosa.de/id/qucosa%3A27732.
Full textAbstract:
Dendritic cells (DCs) are professional antigen-presenting cells, which display an extraordinary capacity to induce T-cell responses. Recent findings revealed that DCs also play a crucial role in the activation of natural killer (NK) cells representing important effectors in the innate immune defense against viruses and tumors. Here, we summarize various studies investigating the bidirectional crosstalk between human DCs and NK cells. In this context, it has been reported that DCs efficiently enhance CD69 expression, proliferation, interferon (IFN)-γ secretion and cytotoxic activity of NK cells. Cell membrane-associated molecules as well as soluble factors such as interleukin-12, tumor necrosis factor-α and type I IFNs contributed to DC-mediated NK cell activation. Reciprocally, the ability of human NK cells to enhance the immunostimulatory capacity of DCs was shown. Thus, NK cells promoted the maturation of DCs and markedly augmented their capacity to produce proinflammatory cytokines and to stimulate T-cell responses. The NK cell-mediated effects on DCs were dependent on cell membrane-associated molecules such as NKp30 and soluble factors such as tumor necrosis factor-α and IFN-γ. In conclusion, the reciprocal activating interaction between human DCs and NK cells may play a pivotal role in the immune defense against viruses and tumors.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Kawamura, Kazuko. "Virus-stimulated plasmacytoid dendritic cells induce CD4[+] cytotoxic regulatory T cells." Kyoto University, 2006. http://hdl.handle.net/2433/143873.
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Tan, Ping, and 陳冰. "Migratory & functional properties of dendritic cells upon interactionswith dying cells & after triggering by inflammatory stimuli." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B45010961.
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Tan, Ping. "Migratory & functional properties of dendritic cells upon interactions with dying cells & after triggering by inflammatory stimuli /." View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36434024.
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Kalogeropoulos, Michail. "Novel mechanisms of dendritic cell regulation by leukocyte immunoglobulin-like receptor B1." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=210082.
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Dendritic cells play an essential role in activating immune responses upon recognition of pathogens. This results in maturation and migration to the lymph nodes, where T cells are stimulated by upregulated antigen presentation, co-stimulation and cytokine secretion. DCs are also considered important in inhibiting inappropriate immune responses against self-peptides which could lead to the development of autoimmunity. This has been attributed to DCs that demonstrate inhibited co-stimulation and cytokine secretion. It has been previously shown that the continuous ligation of an immunomodulatory receptor, LILRB1, during DC differentiation results in such a DC population that demonstrates an immature phenotype even after exposure to bacterial components and resulted in inhibiting primary T cell responses. The mechanisms by which LILRB1-DCs promote tolerance are, therefore, here investigated. Previous studies revealed significantly altered expression for a large number of gene targets which varied from immune to cytoskeletal and bone-related functions. One of these includes DcR3, a soluble protein with a poorly defined role in immune regulation. It is here demonstrated that DcR3 has a positive role in the induction of IL-17, a cytokine implicated in autoimmunity. However, DcR3 was not secreted by LILRB1-DCs, possibly accounting for some of their tolerogenic functions. In addition, the expression of several cytoskeletal proteins was significantly changed in response to LILRB1 ligation and was associated with decreased ability for phagocytosis and migration. Lastly, it has been recently identified that DCs are able to trans-differentiate into osteoclasts, the main cell type linked with inflammatory bone disorders, such as rheumatoid arthritis. It is here shown for the first time that ligation of LILRB1 inhibits this process and results in decreased bone resorption. Overall, these data provides evidence that ligation of LILRB1 on DCs affects normal inflammatory functions and suggests its potential for the development of new treatments against several autoimmune diseases.
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Sarris, Milka. "Dynamics of helper T cell and regulatory T cell interactions with dendritic cells." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611896.
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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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Ho, Christopher Siaw Kang. "Blood dendritic cells in surgery and breast cancer /." [St. Lucia, Qld.], 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18162.pdf.
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