Suppression of human NK cell cytotoxicity by an MLC-Generated cell population

Abstract

A suppressor cell generated in late MLC was capable of inhibiting the cytotoxic activity of fresh NK cells and MLC-generated NK-like cells. Maximum suppression was obtained by using the cells from a 12-day MLC and resulted in a 47% inhibition in fresh NK activity as measured by 51Cr release. The inhibition was also apparent in the single-cell cytotoxicity assay, where suppression was manifested at the level of target recognition. This was reflected in the number of target-binding conjugates (TBC), with a decreased number of TBC consistently found when day 12 MLC cells were added to fresh NK cells or MLC-generated NK-like cells. A soluble suppressive factor generated in MLC did not appear to be the mechanism underlying the suppression, because the addition of the supernatant from a 12-day MLC had no effect on the target binding or cytotoxic activity of fresh NK cells. An adherent cell population was not involved, as the removal of G-10 adherent cells from the day 12 MLC did not alter suppression of NK cytotoxicity. The phenotype of the regulatory cell in the day 12 MLC was Fcmu+ and HNK-1+ (Leu-7). These suppressor cells do not bear antigens detected by monoclonal antibodies to T cells (Leu-4), suppressor T cells (Leu-2a), HLA-DR, or the Fc gamma receptor on NK cells (B73.1). The manner in which the HNK-1+, Fcmu+ suppressor cells exerted their inhibitory effect was by binding directly to Fc gamma +, HNK-1+ fresh NK cells. In turn, the Fc gamma +, HNK-1+ NK cells were rendered incapable of binding to target cells. These results suggest that NK cells themselves can function as immunoregulators, controlling their own cytotoxic activity.