In this work, we identify CD8+ T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs)—the functional counterpart of the mouse Ly49 family in humans (8)—as a regulatory CD8+ T cell subset in humans that suppresses pathogenic CD4+ T cells in celiac disease (CeD) and likely other autoimmune disorders and infectious diseases as well. This evidence concerns the gene CD8A and autoimmune disease.