Abstract
Theophylline, caffeine, and dibutyryl cAMP, agents that elevate intracellular levels of cyclic AMP, were found to inhibit cytotoxin elaboration by PHA-stimulated human lymphocytes. Cytotoxins in diluted supernatants from 3-day lymphocyte cultures were assayed by 51Cr release from L cells. Addition of the agents to the lymphocyte cultures inhibited cytotoxin elaboration 70–90% at 10 −3 M and 20–50% at 10 −5 M. In addition, it was found that the inhibition is reversible and occurs at a step other than the initial mitogen triggering. The inhibition of cytotoxin elaboration by these agents correlates strikingly with their inhibition of lymphocyte-mediated target cell lysis. The results are consistent with the hypothesis that cytotoxin is the mediator of target cell killing by lymphocytes.
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