KIR⁺CD8⁺ and NKG2A⁺CD8⁺ 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 KIR⁺CD8⁺ T cells and NKG2A⁺CD8⁺ T cells. KIRs and NKG2A tend to be expressed by human CD8⁺ T cells in a mutually exclusive manner. In addition, TCR clonotypes of KIR⁺CD8⁺ T cells barely overlap with those of NKG2A⁺CD8⁺ T cells, and KIR⁺CD8⁺ T cells are more terminally differentiated and replicative senescent than NKG2A⁺CD8⁺ T cells. Among cytokine receptors, IL12Rβ1, IL12Rβ2, and IL18Rβ are highly expressed by NKG2A⁺CD8⁺ T cells, whereas IL2Rβ is expressed by KIR⁺CD8⁺ T cells. IL-12/IL-18-induced production of IFN-γ is prominent in NKG2A⁺CD8⁺ T cells, whereas IL-15-induced NK-like cytotoxicity is prominent in KIR⁺CD8⁺ T cells. These findings suggest that KIR⁺CD8⁺ and NKG2A⁺CD8⁺ T cells are distinct innate-like populations with different cytokine responsiveness.