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Early Biochemical Alterations Induced by Lymphotoxin in Target Cells¹

From the Department of Pathology, University of California, San Francisco, California 94143

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.

Footnotes

¹ This work was supported by United States Public Health Service Grant CA 07191-10 and Career Development Award GM-07225-02.

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