Distinct innate-like characteristics of CD8+ T cells expressing KIR or NKG2A

Abstract

Recent studies described that CD8$^+$ T cells expressing inhibitory receptors KIR or NKG2A have innate-like functional capacities to respond to cytokine, perform direct cytotoxicity, or mediate antibody-dependent cellular cytotoxicity (ADCC). Herein, I found that co-expression of KIR and NKG2A is not common and close to 95% of KIR or NKG2A expressing CD8$^+$ T cells expressed only one receptor and I examined the phenotypic and functional difference between KIR$^+$CD8$^+$ T cells and NKG2A$^+$CD8$^+$ T cells. NKG2A$^+$CD8$^+$ T cells had a distinct function of producing IFNγ in response to IL-12 and IL-18, whereas KIR$^+$CD8$^+$ T cells dominated in TCR-independent direct cytotoxicity and ADCC. Furthermore, the major KIR expressing subset was terminally differentiated (CCR7$^-$CD45RA$^+$) and cellular senescent (CD28$^-$CD57$^+$) CD8$^+$ T cells, whereas the major NKG2A+CD8+ T cells were effector memory (CCR7$^-$CD45RA$^-$) and not senescent (CD28$^+$CD57$^-$) CD8$^+$ T cells. In addition, I found that KIR$^+$CD8$^+$ T cells had high T-bet expression and maintained IL-15 responsiveness. However, PLZF was the key transcription factor of NKG2A$^+$CD8$^+$ T cells regulate expression of IL-12 and IL-18 receptors, which make sensitive to cytokine stimulation. Expression of Nur77, a marker of basal TCR interaction, was also increased in NKG2A$^+$CD8$^+$ T cells. Taken together, I demonstrated that different innate-like functions and transcriptional regulation between KIR$^+$CD8$^+$ T cells and NKG2A$^+$CD8$^+$ T cells.