title: 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(-) CD56(bright) 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(-) CD56(dim) NK cells and CD16(-) CD56(bright) NK cells, both of which are less than 1% in PBMC) much more vigorously proliferated after cytokine stimulation, whereas predominant CD16(+) CD56(dim) NK cells proliferated poorly. In addition, many of the resting CD16(-) CD56(bright) NK cells developed into CD16(+) CD56(bright) NK cells, and CD16(-) CD56(dim) NK cells developed into CD16(-) CD56(bright) NK cells and also further into CD16(+) CD56(bright) NK cells by the cytokines. CSFE label experiments further substantiated the proliferation capacity of each subset and the developmental process of CD16(+) CD56(bright) NK cells. Both CD16(-) CD56(dim) NK cells and CD16(-) CD56(bright) NK cells produced large amounts of IFN-gamma and Fas-ligands. The CD16(+) CD56(bright) 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(+) CD56(bright) NK cells was also induced when PBMC were stimulated with penicillin-treated Streptococcus pyogenes, thus suggesting their role in tumour immunity and bacterial infections.
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Kuranaga
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: Y
authors.initials: Y
authors.lastname: Habu
authors.forename: N
authors.initials: N
authors.lastname: Shinomiya
authors.forename: T
authors.initials: T
authors.lastname: Asano
authors.forename: S
authors.initials: S
authors.lastname: Seki
authors.forename: M
authors.initials: M
authors.lastname: Hayakawa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D019002:CD56 Antigen / Q000032:analysis; D016207:Cytokines / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D005452:Fluoresceins / Q000737:chemistry; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000737:chemistry / Q000276:immunology*; D010844:Picibanil / Q000494:pharmacology; D017452:Receptors, IgG / Q000032:analysis; D013297:Streptococcus pyogenes / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D019002:CD56 Antigen; D016207:Cytokines; D005452:Fluoresceins; D015395:Histocompatibility Antigens Class I; D017452:Receptors, IgG; D010844:Picibanil