The effects of cyclic nucleotides on the proliferation of cultured human T-lymphocytes

The effects of cyclic nucleotides on the proliferation of cultured T-lymphocytes (CTC) stimulated by either phytohemagglutinin (PHA) or lectin-free interleukin-2 (IL-2) were studied. The addition of either N6,O2-dibutyryl cyclic AMP (DB-cAMP), aminophylline or isoproterenol to CTC cultures significantly suppressed the proliferation of CTC stimulated by either PHA or IL-2. This inhibitory effect was maximal when added at initiation of the assay; however, significant depression was still observed when added 24 h later. When DB-cAMP and aminophylline were added together, the inhibitory effects were additive. When DB-cGMP was added to the CTC cultures, inhibition of both PHA- and IL-2-stimulated cultures was also found, but the degree of activity was considerably less than for DB-cAMP or aminophylline. In contrast, when carbachol was added, no inhibition or modulation in proliferation was seen. Lastly, DB-cGMP was not found to antagonize the inhibitory effect of DB-cAMP, but instead to further increase the level of inhibition. In summary, these studies illustrate that cyclic nucleotides modulate the proliferation of IL-2-stimulated CTC as well as PHA-treated cells. This model system should provide an approach to study, in more depth, the mechanism by which cyclic nucleotides or their inducers can modulate the latter stages of the lymphocyte proliferative response, which is mediated by the lymphokine, IL-2.