BLOCK OF T-LYMPHOCYTE DIFFERENTIATION BY ACTIVATION OF THE CAMP-DEPENDENT SIGNAL-TRANSDUCTION PATHWAY

Differentiation of T lymphocytes is a complex and finely tuned process , Here we show that treatment of mouse fetal thymus organ cultures wit h agents activating the cAMP-dependent signalling pathway results in t he block of thymocyte differentiation. This is due to severe impairmen t of maturation beyond the CD4-/CD8- stage. In addition, rearrangement s at the TCR alpha gene locus, but not at the TCR beta locus, are comp letely inhibited, The cAMP effect is reversible and is restricted to T CR alpha beta+ cells, cAMP acts both by triggering apoptosis and by in ducing cell-cycle block in thymocytes, Thus, activation of the cAMP pa thway provides a mechanism to modulate thymic function for hormones an d ligands whose receptors are coupled to adenylate cyclase.