Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro

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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.

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