Effect of interleukin-2 on the monomeric IgG-induced inhibition of human natural killer cell activity

Monomeric IgG (mIgG) has been previously shown to inhibit human natural killer (NK) cell activity when effector cells were treated prior to the cytotoxic assay. In the present study the interaction between negative regulation by mIgG and positive regulation by interleukin-2 (IL-2) was examined. Although a dose-dependent boosting of NK activity was found upon incubation of nonadherent lymphocytes (NAL) with recombinant or natural IL-2 for 2 h at 37 degrees C, the NK effector cells remained responsive to down-regulation to mIgG. However, when NAL were treated with IL-2 under supraoptimal conditions (higher doses and longer periods of incubation than required for optimal boosting of NK activity) the subsequent addition of mIgG had a significantly reduced inhibitory effect. This partial resistance to suppression by inhibitory IgG was observed only when the second treatment was performed without washing the IL-2-pretreated effector cells. Moreover, addition of antihuman interferon gamma antibodies during the incubation of NAL with IL-2 almost abolished the loss of responsiveness of the IL-2-activated killer cells to mIgG-induced inhibition. These data provide additional evidence for the ability of interferon gamma to reverse or block the down-regulation of NK activity by mIgG.