Immunological tolerance is maintained by self-reactive CD8 T cells

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.