Early Biochemical Alterations Induced by Lymphotoxin in Target Cells

Abstract Lymphocyte-mediated target cell destruction apparently involves a cytotoxic protein, lymphotoxin, produced by antigen- or mitogen-stimulated lymphocytes. Various biochemical functions of L cells exposed to purified lymphotoxin were examined. No alterations in glycolysis, oxidative phosphorylation or Na-K pump were observed. Nor does lymphotoxin-induced cytolysis appear to be mediated by lysolecithin. In contrast to these negative findings, an early decrease in the number of polysomes and a marked increase in the rate of RNA synthesis were detected. The cytotoxic effect of lymphotoxin is greatly potentiated and accelerated by actinomycin D, even at early intervals, when this inhibitor per se causes little cytotoxicity. The ability to potentiate the effect of lymphotoxin would be particularly important in tumor immunity, where accentuation of the relatively weak immune resonse might be beneficial to the host.