Self-originating CTL peptides induce the cross-activation of Treg cells to suppress the proliferation of self-reactive CD8(+) T cells

초록

Most of self-reactive T cells are eliminated by the central tolerance in thymus, but some of T cells with low TCR affinity survived from the central tolerance are controlled by peripheral tolerance. Although multiple factors are involved in the peripheral tolerance, the balance between Treg and effector T cells seems to be a key player in maintaining the peripheral tolerance. Here we found that cytotoxic CD8+ T cell-restricted (CTL) peptides originating from self-tumor antigens including hTERT, WT-1 and Malan-A not only induced the proliferation of CD8+ T cells, but also induced the activation and division of Foxp3+ Treg cells with a delayed kinetics. Proliferation of self-reactive CD8+ T cells were swiftly induced by the CTL peptides during the initial phase of culture, but suppressed by the expanded Treg cells in the latter phase. Cross-activation of Tregs by CTL peptides originating self Ags is not found when the CD8+ T cells specific to cytomegalovirus (CMV) antigen. These finding indicate that CTL peptides originating self Ags have a potential to activate both CD8+ T cells and Treg cells and thus, limit the T cell-mediated autoimmune responses.