| Abstract: | The Fcγ receptor (R)IIIA (CD16) 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 FcγRIIIA, 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 FcγRIIIA 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-2Rα, ICAM-1), cytotoxicity, cytokine production (IL-1β, IFN-γ and TNF-α) and release of soluble IL-2R. Thus, mIgG binding to FcγRIIIA induced stimulatory signals in human NK cells, leading to up-regulation of IL-2Rα expression, cell proliferation and cytokine release. |
