CYCLIC-AMP AND T-CELL DIFFERENTIATION

The effects of a circulating thymic factor (TF), cyclic(c)AMP and prostaglandins on T[thymus-derived]-lymphocyte differentiation was studied in the mouse using 3 parameters: .theta.-bearing cell percentage evaluated by a cytotoxicity test with anti-.theta. serum (A.theta.S) plus complement; .theta.-antigen presence on rosette forming cells (RFC) assessed by the inhibition of rosette formation with A.theta.S; lymphocyte mediated cytotoxicity (LMC) against allogeneic target cells [mastocytoma P-815 cells] after in vivo sensitization, using a Cr release assay. These 3 parameters were affected by adult thymectomy: the .theta.-bearing cell percentage was lowered in the spleen, spleen RFC became resistant to inhibition by A.theta.S, and LMC was diminished. TF increased (in vivo or in vitro) the sensitivity of RFC from thymectomized (Tx) mice to A.theta.S inhibition up to the normal level. In vivo TF treatment also normalized the depressed LMC reaction of Tx mice. AMP and agents increasing its intracellular concentration (such as prostaglandins) also corrected the abnormal resistance of RFC from the spleen of Tx mice to A.theta.S. Adenylate cyclase stimulation is probably involved in the mode of action of TF on T-lymphocyte maturation. Normal mice treated with indomethacin, a prostaglandin-synthetase inhibitor, showed similar abnormalities to those induced by adult thymectomy: .theta.-bearing cell percentage was lowered in the spleen and there was less sensitivity of RFC to A.theta.S. LMC against allogeneic cells was also depressed. TF effects on lymphocyte differentiation could be mediated by prostaglandins as well as by cAMP.