Inhibition of human natural killer cell activity by cytophilic immunoglobulin G

The natural killer (NK) cell activity of human peripheral blood mononuclear cells (PBL) was found to be increased after incubation at 37 degrees C for 2 hr. The observed increase was shown to be associated with release from inhibition by human serum factors, because incubation in autologous serum interfered with augmentation. The serum-mediated effect appeared attributable to the degree of binding of labile IgG to PBL and could be reduced by selective depletion of IgG from the serum. Human monomeric IgG was found to efficiently inhibit the culture-induced augmentation of NK activity; the inhibitory IgG had properties consistent with those described for cytophilic IgG and was mediated through the Fc region of IgG. The inhibition by monomeric IgG occurred at 0 degrees C as well as at 37 degrees C and this could be induced even after culture-induced augmentation of NK activity. Thus, binding of monomeric IgG to human PBL appears to reversibly inhibit their NK activity. These results provide evidence for a novel mechanism for negative regulation of NK activity.