Regulation of susceptibility to natural killer cells' cytotoxicity and regulation of HLA synthesis: differing efficacies of alpha, beta, and gamma interferons.
Interferon (IFN) is an effective activator of the natural killer (NK) cells but can also induce, in a variety of target cells, resistance to the NK induced cytolysis. We have compared the ability of the various types of human IFN to carry out this function, by quantitating the cytolysis induced by NK cells in cultured fibroblasts pretreated with each IFN and comparing this effect of the IFNs to their effectivity in suppressing viral replication. Relative to their antiviral potency, preparations of IFN-gamma were significantly more effective than the alpha or beta interferons in inducing what we call the "anti-NK" effect. Significant inhibition of the natural killing was observed with IFN-gamma even at concentrations at which no antiviral effect was induced. Preparations of IFN-gamma were also more effective than the other interferons in suppressing cell growth. While the induction of the enzyme oligo-isoadenylate synthetase correlated to the antiviral effectivity of the interferons, the quantitation of the HLA proteins in the cells had shown that their induction by the interferons correlates to the induction of the anti-NK effect, being stimulated much more effectively by IFN-gamma than by IFN-alpha or IFN-beta. The anti-NK, HLA and antiviral-inducing activities co-purified in fractionation of IFN-gamma preparations. These findings suggest the existence of several independent mechanisms for the regulation of cell functions by interferons. The gamma IFN is particularly effective in regulating functions involved in the interaction of cells with the immune system while the gamma virus-induced IFN-alpha and -beta are more effective as inducers of resistance to viral growth.
D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005347:Fibroblasts / Q000276:immunology; D006680:HLA Antigens; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D014762:Viral Interference
D006680:HLA Antigens; D007370:Interferon Type I; D007371:Interferon-gamma; D007372:Interferons