KIR(+)CD8(+) T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19

In this work, 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 the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIR(+)CD8(+) T cells, but not CD4(+) regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis. Selective ablation of Ly49(+)CD8(+) T cells in virus-infected mice led to autoimmunity after infection. Our results indicate that in both species, these regulatory CD8(+) T cells act specifically to suppress pathogenic T cells in autoimmune and infectious diseases.