The Inhibition of the Mixed Lymphocyte Culture Reaction by Cyclic Adenosine 3′,5′-Monophosphate 1

Abstract

Summary

Prostaglandin E₁, theophylline and dibutyryl cyclic AMP uniformly suppressed the [³H]thymidine incorporation in human mixed lymphocyte culture in a dose dependent manner. The inhibitory effects were time dependent, with the maximum when the agents were added at the time of the initiation of the culture, decreasing gradually when added at 24 hr, 48 hr and 72 hr and becoming undetectable when added at 96 hr or later. When prostaglandin E₁ and theophylline or dibutyryl cyclic AMP and theophylline were added together an additive effect was found. Dibutyryl cyclic AMP also inhibited the stimulation of protein synthesis in mixed lymphocyte culture. It is concluded that the T-cell response in the MLC reaction is modulated by the intracellular level of cyclic AMP as observed with a variety of other immune reactivities.