Induction of CD16+ CD56bright NK cells with antitumour cytotoxicity not only from CD16- CD56bright NK cells but also from CD16- CD56dim NK cells

Abstract

The aim of this study was to examine the effect of cytokines on different subsets of NK cells, while especially focusing on CD16- CD56 dim cells and CD16- CD56bright cells. When human peripheral blood mononuclear cells (PBMC) were cultured with a combination of IL-2, IL-12 and IL-15 for several days, a minor population of CD56 bright NK cells expanded up to 15%, and also showed potent cytotoxicities against various cancer cells. Sorting experiments revealed that unconventional CD16- CD56+ NK cells (CD16- CD56dim NK cells and CD16- CD56bright NK cells, both of which are less than 1% in PBMC) much more vigorously proliferated after cytokine stimulation, whereas predominant CD16+ CD56dim NK cells proliferated poorly. In addition, many of the resting CD16- CD56bright NK cells developed into CD16+ CD56 bright NK cells, and CD16- CD56dim NK cells developed into CD16- CD56bright NK cells and also further into CD16+ CD56bright NK cells by the cytokines. CSFE label experiments further substantiated the proliferation capacity of each subset and the developmental process of CD16+ CD56bright NK cells. Both CD16- CD56dim NK cells and CD16- CD56bright NK cells produced large amounts of IFN-γ and Fas-ligands. The CD16+ CD56bright NK cells showed strong cytotoxicities against not only MHC class I (-) but also MHC class I (+) tumours regardless of their expression of CD94/NKG2A presumably because they expressed NKG2D as well as natural cytotoxicity receptors. The proliferation of CD16 + CD56bright NK cells was also induced when PBMC were stimulated with penicillin-treated Streptococcus pyogenes, thus suggesting their role in tumour immunity and bacterial infections. © 2007 The Authors.