Li J, Zaslavsky M, Su Y, Guo J, Sikora MJ, van Unen V, Christophersen A, Chiou SH, Chen L, Li J, Ji X, Wilhelmy J, McSween AM, Palanski BA, Mallajosyula VVA, Bracey NA, Dhondalay GKR, Bhamidipati K, Pai J, Kipp LB, Dunn JE, Hauser SL, Oksenberg JR, Satpathy AT, Robinson WH, Dekker CL, Steinmetz LM, Khosla C, Utz PJ, Sollid LM, Chien YH, Heath JR, Fernandez-Becker NQ, Nadeau KC, Saligrama N, Davis MM.
Science, 8 March 2022

Here we find that CD8+ T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49+CD8+ regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8+ T cells efficiently eliminated pathogenic gliadin-specific CD4+ T cells from celiac disease patients’ leukocytes in vitro. We also find elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 patients, which correlated with disease severity and vasculitis. Selective ablation of Ly49+CD8+ T cells in virus-infected mice led to autoimmunity post infection. Our results indicate that in both species, these regulatory CD8+ T cells act uniquely to suppress pathogenic T cells in autoimmune and infectious diseases.