Mechanisms of lymphocyte activation: linkage between early protein synthesis and late lymphocyte proliferation

An experimental model has been developed to study the mechanisms of lymphocyte activation. Using this model we examined the relationship between early protein synthetic events and the late proliferative response to Con A. We found that transient puromycin or cycloheximide-induced inhibition of protein synthesis during the first hour of stimulation by Con A resulted in either inhibition or enhancement of the response, depending on the subsequent treatment of the cells. If the lymphocytes were either not restimulated or restimulated immediately after the initial pulse with metabolic inhibitor plus Con A, there was a decrease in the proliferative response. However, if the cells were restimulated with Con A 24 hr later, there was a shift in the kinetics resulting in a prolonged and increased response. Inhibition of protein synthesis at 6 hr after stimulation with Con A produced no noticeable effects. Hence, there are protein synthetic events that take place during the first hours of stimulation that are critical for the development of the proliferative response. The possibility that these early protein synthetic events are the target for macrophage-mediated regulation of lymphocyte function is discussed.