title: Divergent effects of Fc gamma RIIIA ligands on the functional activities of human natural killer cells in vitro.
abstract: The Fc gamma receptor (R)IIIA (CD 16) plays an important role in regulating the cytotoxic and non-cytotoxic functions of human natural killer (NK) cells. Some anti-CD 16 monoclonal antibodies (mAb) have been shown to stimulate NK activity, while human monomeric (m) IgG induces dose-dependent inhibition of NK activity. To explore further these interactions mediated via Fc gamma RIIIA, purified NK cells were cultured for 2-3 days in the presence of mIgG, 3G8 mAb, interleukin-2 (IL-2) or a combination of mIgG or 3G8 with IL-2. Binding of mIgG or 3G8 to Fc gamma RIIIA induced divergent effects of functions of cultured NK cells: 3G8 mAb + IL-2 induced dose-dependent inhibition of proliferation attributable to apoptosis; in contrast, mIgG + IL-2 significantly increased NK cell proliferation. Incubation of NK cells in the presence of mIgG up-regulated expression of surface activation markers (CD69, IL-2R alpha, ICAM-1), cytotoxicity, cytokine production (IL-1 beta, IFN-gamma and TNF-alpha) and release of soluble IL-2R. Thus, mIgG binding to Fc gamma RIIIA induced stimulatory signals in human NK cells, leading to up-regulation of IL-2R alpha expression, cell proliferation and cytokine release.
authors.affiliation: Center for Immunology, Institute of Virology, Bucharest, Romania.
authors.forename: A
authors.initials: A
authors.lastname: Sulica
authors.forename: D
authors.initials: D
authors.lastname: Metes
authors.forename: M
authors.initials: M
authors.lastname: Gherman
authors.forename: T L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: R B
authors.initials: RB
authors.lastname: Herberman
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012995:Solubility
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D007074:Immunoglobulin G; D007376:Interleukin-2; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2