Role of cyclic nucleotides in human lymphocyte-mediated antibody-dependent cytotoxicity

Experiments were carried out in order to throw light on the role of cyclic AMP and cyclic GMP in the modulation of the expression of antibody-dependent cytotoxicity mediated by human peripheral blood lymphocytes in vitro. Chicken erythrocytes were used as target cells. Support for an inhibitory role of cyclic AMP was derived from the marked suppression of cytotoxicity by dibutyryl cyclic AMP. Cyclic AMP itself had little effect. Isoproterenol, prostaglandin E1 and prostaglandin E2 increased cyclic AMP concentrations and strongly inhibited the cytotoxic effect of the lymphocytes. Histamine showed very slight elevation of the cyclic AMP level and suppression of the cytotoxicity. Theophylline did not increase the cyclic AMP concentration, but potentiated the effects of isoproterenol and prostaglandin E1 on the cyclic AMP levels, and significantly inhibited cytotoxicity. No clear effects were seen when cyclic GMP, dibutyryl GMP, acetylcholine or carbacholine were added to the cells. The results indicate that in this system cyclic AMP inhibits cytotoxicity, while no evidence for a role of cyclic GMP has been obtained.