Previous reports show that Ly49 CD8 T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8 T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalent of the Ly49 family, in the blood and inflamed tissues of various autoimmune diseases. Moreover, KIR CD8 T cells can efficiently eliminate pathogenic gliadin-specific CD4 T cells from Celiac disease (CeD) patients' leukocytes . Furthermore, we observe elevated levels of KIR CD8 T cells, but not CD4 regulatory T cells, in COVID-19 and influenza-infected patients, and this correlates with disease severity and vasculitis in COVID-19. Expanded KIR CD8 T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8 T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells.

Human KIR + CD8 + T cells target pathogenic T cells in Celiac disease and are active in autoimmune diseases and COVID-19