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.
2025-09-01 | GSE276189 | 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.
2025-08-30 | GSE276227 | GEO
Project description:Immunological tolerance is maintained by self-reactive CD8 T cells
| PRJNA1452731 | ENA
Project description:CD8 T cells play a critical role in immune tolerance maintenance after immune activation. They have recently been reported to target activated CD4 T cells in an MHC-Ia–restricted manner. However, the specific peptides and the corresponding reactive CD8 TCRs responsible for this targeting process remain unknown. In this study, we identified the self-peptides on activated CD4 T cells, cloned the corresponding CD8 TCRs, and validated the in vitro and in vivo immunosuppressive function of CD8 T cells carrying these self-reactive TCRs. The therapeutic potential of peptide vaccination and self-reactive CD8 T cells was confirmed in a mouse model of experimental autoimmune encephalitis (EAE). This study consequently redefines the nature of CD8 regulatory T (Treg) cells as self-reactive CD8 T cells.
2026-04-13 | GSE327753 | 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:Preventing autoantibody secretion by rendering self-reactive B cells functionally silent through clonal anergy has long posed the question of why fill the circulating B cell repertoire with cells that cannot secrete antibody? Here we address this question from the perspective of B cells that comprise 5-10% of the human circulating repertoire, expressing self-reactive surface immunoglobulins employing the IGHV4-34 heavy chain variable element. Using gene targeting to construct mice expressing a representative human IGHV4-34 antibody on the surface of many B cells, we show these cells are prevented from autoantibody secretion by B cell clonal anergy marked by downregulation of surface IgM, induction of tolerance-response mRNAs, and exclusion from the marginal zone and B1 cell subsets. This functionally tolerant state is overridden when the IGHV4-34 B cells cross-react with a virus, which stimulates the self-reactive B cells to hypermutate in germinal centres. Within 16 days of infection, 99% of daughter cells have acquired one of five heavy chain mutations that diminish binding to self but preserve virus binding, and 33% had combined 2 or 3 of these mutations to become genetically self-tolerant and virus specific. These results demonstrate, from the perspective of a pathologically important human autoantibody class and the world’s most successful virus vaccine, how human antibody specificity is sculpted in the progeny of anergic B cells to yield antibodies that bind a virus but not self.
2026-01-12 | GSE308256 | GEO
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