Induction of CD16+ CD56bright NK Cells with Antitumour Cytotoxicity not only from CD16 CD56bright NK Cells but also from CD16 CD56dim NK Cells

Authors


S. Seki, MD, Department of Immunology and Microbiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. E-mail: btraums@res.ndmc.ac.jp

Abstract

The aim of this study was to examine the effect of cytokines on different subsets of NK cells, while especially focusing on CD16 CD56dim 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 CD56bright 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+ CD56bright 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.

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