Potentiation of cytokine-induced proliferation of human Natural Killer cells by intravenous immunoglobulin G.

Intravenous IgG (IVIG) therapy can be used for immunomodulation. IL-2 is an immunoregulatory cytokine. We evaluated IVIG modulation of human blood lymphocyte response to IL-2 and other cytokines. Neither IVIG nor low concentrations of IL-2 (3-30U/ml) induced lymphocyte proliferation, but in combination they synergistically enhanced proliferation of NK cells. The CD56(bright) cells expanded more than CD56(dim) NK cells, with 90% of NK cells dividing up to 8 generations by day 6, while <8% of T cells divided. IVIG also potentiated NK cell proliferation with IL-12, IL-15 and IL-18. The IVIG+cytokine-expanded NK cells were less cytotoxic for K562 cells, than NK cells with cytokine alone. IVIG also enhanced interferon-γ production with IL-2, IL-12 and IL-18. In conclusion, IVIG selectively potentiates NK cell proliferation and interferon-γ secretion with IL-2, IL-12, IL-15 and IL-18 in vitro. These findings warrant evaluation in vivo in relation to NK cells and the immunoregulatory actions of IVIG.