Antagonistic effects of interferons on the cytotoxicity mediated by natural killer cells

Abstract

Human interferons (IFs) can induce a several-fold increase in the natural cytotoxicity of human lymphocytes on target cell lines. IFs increase the efficiency of cytotoxicity and the number of natural killer (NK) cells. In mixed cultures of lymphocytes and other tumor-derived or virus-infected cells, endogenous IF is produced, which mediates 70-90% of the observed cytotoxicity. The effect of IF on target cells is antagonistic to its effect on lymphocytes: the susceptibility to lysis of cells treated with IF decreases. Whereas normal fibroblasts are protected by IF, virus-infected cells and most tumor-derived cells are not. The protective effect is specific for NK cells cytotoxicity: IF-treated target cells are lysed to the same extent as the untreated controls by antibody-dependent killer cells, by phytohemagglutinin-stimulated lymphocytes, by cytotoxic T lymphocytes, and by antibodies and complement. NK cells bind to IF-treated fibroblasts, but are unable to lyse them. The cytotoxic ability of NK cells is inactivated after interaction with normal fibroblasts, but not with IF-treated fibroblasts. Unlabeled, normal fibroblasts but not IF-treated fibroblasts compete for the cytotoxicity mediated by NK cells in 51Cr-labeled target fibroblasts. IF, by stimulating very efficient, nonspecific cytotoxic cells, and by protecting normal cells from lysis, might render the NK cell system an inducible defense mechanism against virus-infected and tumor cells.