Detection of self-reactive CD8 + T cells with an anergic phenotype in healthy individuals

• DOI: 10.1126/science.aaa1292
• Publication Date: 2014-12-19T08:12:06Z
• Authors: Yuka Maeda; Hiroyoshi Nishikawa; Daisuke Sugiyama; Danbee Ha; Masahide Hamaguchi; Takuro Saito; Megumi Nishioka; James B. Wing; Dennis Adeegbe; Ichiro Katayama; Shimon Sakaguchi
• Keywords: Clonal Anergy; 0301 basic medicine; Receptors, Antigen, T-Cell; Vitiligo; Antigen-Presenting Cells; CD8-Positive T-Lymphocytes; Lymphocyte Activation; T-Lymphocytes, Regulatory; Autoimmune Diseases; 3. Good health; 03 medical and health sciences; Self Tolerance; Humans; CTLA-4 Antigen

Immunological tolerance to self requires naturally occurring regulatory T (T reg ) cells. Yet how they stably control autoimmune T cells remains obscure. Here, we show that T reg cells can render self-reactive human CD8 + T cells anergic (i.e., hypoproliferative and cytokine hypoproducing upon antigen restimulation) in vitro, likely by controlling the costimulatory function of antigen-presenting cells. Anergic T cells were naïve in phenotype, lower than activated T cells in T cell receptor affinity for cognate antigen, and expressed several coinhibitory molecules, including cytotoxic T lymphocyte–associated antigen-4 (CTLA-4). Using these criteria, we detected in healthy individuals anergic T cells reactive with a skin antigen targeted in the autoimmune disease vitiligo. Collectively, our results suggest that T reg cell–mediated induction of anergy in autoimmune T cells is important for maintaining self-tolerance.