The CD56bright CD62L+ NKG2A+ immature cell subset is dominantly expanded in human cytokine-induced memory-like NK cells

Abstract

Recent studies have revealed immunological memory of NK cells. Short-term in vitro cytokine stimulation also induces NK cell memory, but heterogeneous cell subsets within the cytokine-induced memory-like (CIML) NK cells has not been elucidated. Here we found that the dominant cell subset in human CIML NK cells are immature CD56bright CD62L+cells, and they were selectively expanded CD56bright CD16- CD62L+ NK cells. Although these cells acquired KIR expression after the cytokine stimulation, sustained NKG2A expression inhibits cytotoxicity against HLA-E+ target cells. In contrast, another checkpoint molecule LAG-3 is induced mainly on KIR+ NKG2C+ minor CIML NK cells. Our findings imply targeting NKG2A and LAG-3 should be considered for CIML NK cell-based immunotherapy.