KIRCD8 and NKG2ACD8 T cells are distinct innate-like populations in humans.

Subsets of the human CD8 T cell population express inhibitory NK cell receptors, such as killer immunoglobulin-like receptors (KIRs) and NKG2A. In the present study, we examine the phenotypic and functional characteristics of KIRCD8 T cells and NKG2ACD8 T cells. KIRs and NKG2A tend to be expressed by human CD8 T cells in a mutually exclusive manner. In addition, TCR clonotypes of KIRCD8 T cells barely overlap with those of NKG2ACD8 T cells, and KIRCD8 T cells are more terminally differentiated and replicative senescent than NKG2ACD8 T cells. Among cytokine receptors, IL12Rβ1, IL12Rβ2, and IL18Rβ are highly expressed by NKG2ACD8 T cells, whereas IL2Rβ is expressed by KIRCD8 T cells. IL-12/IL-18-induced production of IFN-γ is prominent in NKG2ACD8 T cells, whereas IL-15-induced NK-like cytotoxicity is prominent in KIRCD8 T cells. These findings suggest that KIRCD8 and NKG2ACD8 T cells are distinct innate-like populations with different cytokine responsiveness.