The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 140, 837-852, Copyright © 1974 by The Rockefeller University Press

ARTICLE

ON THE RELATION OF PRODUCTS OF ACTIVATED LYMPHOCYTES TO CELL-MEDIATED CYTOLYSIS

Christopher S. Henney 1, Judith Gaffney 1, and Barry R. Bloom 1

1 From the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, the O'Neill Memorial Research Laboratories, Good Samaritan Hospital, Baltimore, Maryland 21239, and the Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461

Experiments have been designed to test the hypothesis that soluble mediator production and T-cell-mediated cytotoxicity are necessarily related phenomena, and that soluble mediators may be involved in the mechanism of cytolysis. To this end, agents known to inhibit T-cell-mediated lysis in vitro have been studied for their effects on the production of two lymphocyte-derived mediators, lymphotoxin (LT) and migration inhibitory factor (MIF).

A clear dissociation between mediator production and cell-mediated cytolysis was found using inhibitors of protein synthesis. Pactamycin and emetine, in doses of 10–7 M to 10–6 M, suppressed production of MIF and LT with only slight effect on killing of mastocytoma cells by immune T cells. On the other hand colchicine and vinblastine inhibited T-cell-mediated cytolysis in a dose-related manner but had no significant effect on either MIF or LT production, A striking dichotomy was also observed after augmentation of intracellular cyclic 3'5' adenosine monophosphate (cAMP) levels with cholera enterotoxin. Increased cAMP levels were associated with abrogation of direct lytic activity, but were without significant effect on MIF or LT production in guinea pigs or mice. These findings indicate that mediator production and direct lymphocyte-mediated cytolysis can be experimentally dissociated and represent independent cell-mediated immune functions.

 Submitted on June 4, 1974


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