Self-tolerance maintained by self-reactive CD8+ T cells
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ABSTRACT:
PROVIDER: PRJNA1156020 | ENA |
REPOSITORIES: ENA
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Project description:Self-tolerance maintained by self-reactive CD8+ T cells
| PRJNA1155661 | ENA
Project description:CD8+ T cells play a critical role in immune tolerance maintainnance after immune activation. It is known to function through targeting activated CD4+ T cells, in both Qa-1- and MHC-Ia-restricted9 manner. However, the exact nature of this targeting process, i.e., the specific peptides and the corresponding reactive CD8 TCRs, remains unknown. In this study, we identified the self-peptides on activated CD4+ T cells that could mediate the CD8+ T cells immunosuppressive activity. By cloning the corresponding CD8 TCRs and the generation of TCR transgenic mice , we were able to validate the immunosuppressive function of CD8+ T cells carrying the self-reactive TCRs both in vitro and in vivo. The therapeutic potential of peptide vaccination and CD8+ T cell transfer were confirmed in a mouse EAE model. This study suggest that self-tolerance can be maintained by self-reactive CD8+ T cells recognizing self-antigenic peptides through specific TCRs, thus redefine the nature of CD8+ regulatory T cells as self-reactive CD8+ T cells.
2025-08-30 | GSE276227 | GEO
Project description:CD8+ T cells play a critical role in immune tolerance maintainnance after immune activation. It is known to function through targeting activated CD4+ T cells, in both Qa-1- and MHC-Ia-restricted9 manner. However, the exact nature of this targeting process, i.e., the specific peptides and the corresponding reactive CD8 TCRs, remains unknown. In this study, we identified the self-peptides on activated CD4+ T cells that could mediate the CD8+ T cells immunosuppressive activity. By cloning the corresponding CD8 TCRs and the generation of TCR transgenic mice , we were able to validate the immunosuppressive function of CD8+ T cells carrying the self-reactive TCRs both in vitro and in vivo. The therapeutic potential of peptide vaccination and CD8+ T cell transfer were confirmed in a mouse EAE model. This study suggest that self-tolerance can be maintained by self-reactive CD8+ T cells recognizing self-antigenic peptides through specific TCRs, thus redefine the nature of CD8+ regulatory T cells as self-reactive CD8+ T cells.
2025-09-01 | GSE276189 | GEO
Project description:Self-specific CD8+ T cells often escape clonal deletion, but the properties and capabilities of such cells in a physiological setting are unclear. We characterized polyclonal CD8+ T cells specific for the melanocyte antigen tyrosinase-related protein 2 (Trp2) in mice that express or lack this enzyme due to deficiency in Dct, which encodes Trp2. The size, phenotype, and gene expression profile of the pre-immune Trp2/Kb-specific pool were similar in wild-type (WT) and Dct-deficient (Dct-/-) mice. Despite comparable initial responses to Trp2 immunization, WT Trp2/Kb-specific cells showed blunted expansion, and scRNAseq revealed WT cells less readily differentiated into a CD25+ proliferative population. Functional self-tolerance clearly emerged when assessing immunopathology: adoptively transferred WT Trp2/Kb-specific cells mediated vitiligo much less efficiently. Hence, CD8+ T cell self-specificity is poorly predicted by precursor frequency, phenotype or even initial responsiveness, while deficient activation-induced CD25 expression and other gene expression characteristics may help to identify functionally tolerant cells.
2021-04-30 | GSE171221 | GEO
Project description:Transcriptome in naturally-occuring self-reactive thymocytes
| PRJNA1172123 | ENA
Project description:Non-deletional CD8+ T cell self-tolerance permits responsiveness but limits tissue damage
| PRJNA718819 | ENA
Project description:Genomewide microarray analysis of murine tolerant, self-antigen specific CD8 T cells to identify genes and pathways underlying peripheral T cell tolerance Gene signature of tolerant CD8 T cells was compared to the signatures of naïve T cells, memory T cells, rescued T cells (=tolerant T cells undergoing homeostatic proliferation in lymphopenic, tolerogenic Alb:GAG mice), and re-tolerized T cells (=previously rescued T cells post homeostatic proliferation isolated from lymphoreplete wild-type B6 mice). Total RNA obtained from various sort-purified transgenic CD8 T cell subsets (naïve, memory, tolerant, rescued, and re-tolerized) isolated from spleens of different host mice
2012-02-16 | E-GEOD-32025 | biostudies-arrayexpress
Project description:DNA accessibility in reactive and non-reactive CMV specific CD8+ lymphocytes
| PRJNA413763 | ENA
Project description:Poor immune reconstitution following haematopoietic stem cell transplantation (HSCT) can cause unwanted and harmful sequelae in recipients with chronic cytomegalovirus (CMV) infection. To understand the molecular mechanisms underlying poor reconstitution, we profiled the transcriptome-chromatin accessibility landscape of CMV-specific CD8+ memory lymphocytes from HCST recipients with different reconstitution efficiencies. Although the transcriptional and epigenomic signatures in non-reactive lymphocytes were not naïve or classic ‘exhaustion’ profiles, some gene expression was common to lymphocytes from other non-resolving infections. Reactive lymphocytes expressed higher levels of interferon/defence response and cell cycle genes in an interconnected network involving PI3KCG, STAT5B, NFAT, RBPJ, and NR3C1, increasing chromatin accessibility at the enhancer regions of immune and T cell receptor signalling pathway genes. We propose that increased HDAC6 expression in non-reactive lymphocytes decreases accessibility at particular enhancers including PI3KCG. Non-reactive cells also expressed higher levels of EGR and KLF factors that, along with lower expression of JARID2, maintained higher accessibility at promoter and CpG-rich regions of genes associated with apoptosis. Together, transcription factors and chromatin modulators create a different chromatin accessibility landscape in reactive and non-reactive cells that not only affects immediate gene expression but differentially primes the cells for responses to additional signals.
2018-04-09 | GSE104750 | GEO
Project description:Role for naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) in counterbalancing this process. Using a transgenic murine model for autoimmune-mediated lung disease, we demonstrated that, despite pulmonary inflammation, lung-specific CD8+ T cells can reside quiescently in close proximity to self-antigen. Whereas self-reactive CD8+ T cells in the inflamed lung and lung-draining lymph nodes down-regulated the expression of effector molecules, those located in the spleen appeared to be partly antigen-experienced and displayed a memory-like phenotype. Since ex vivo-reisolated self-reactive CD8+ T cells were very well capable to respond to the antigen in vitro, we investigated a possible contribution of nTregs to the immune control over autoaggressive CD8+ T cells in the lung. We isolated antigen-specifc CD8+ T-cells from lungs and bronchial lymphnodes derived from chronic diseased mice (SPC-HAxCL4), healthy control mice (CL4) and acute influenza infected control mice (CL4+IAV) and perormed mRNA expression profiling of isolated CD8+ T cells. Each group represents a pool of at least n=4 animals. CD8+ T cell type comparison; lung disease state analysis
2011-12-21 | E-GEOD-27379 | biostudies-arrayexpress