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.