Self-tolerance maintained by self-reactive CD8+ T cells

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. Overall design: To investigate the gene expression changes in CD4+ T cells before and after activation, we stimulated C57/B6 mouse splenocytes with 1 µg/ml ConA for 48 hours, then sorted the CD4+ T cells from both the stimulated and unstimulated groups.Then we performed gene expression profiling analysis using data obtained from RNA-seq of stimulated and unstimulated CD4+ T cells.