CAMP ANALOGS PREVENT ACTIVATION-INDUCED APOPTOSIS OF T-CELL HYBRIDOMAS

Activation of T cell hybridomas through their TCR leads to secretion o f IL-2, inhibition of proliferation, and apoptosis. The identification of various inhibitors that prevent activation-induced T cell death (A ICD) has helped identify several essential events in apoptosis. For ex ample, inhibition of AICD by dexamethasone indicates a connection betw een these two programmed death pathways. In this study, we have invest igated the interaction between the cAMP signal transduction pathway an d the activation- or glucocorticoid-induced cell death. cAMP induced D NA fragmentation in thymocytes. T cell hybridomas displayed different sensitivity to cAMP. Regardless of its cAMP sensitivity, programmed ce ll death promoted by anti-CD3 or Ag in hybridoma was prevented by the presence of cAMP analogs. In contrast, cAMP had no effect on glucocort icoid-induced T cell death. The inhibitory effect of cAMP on AICD was unlikely to be due to quenching of T cell activation signals, because cAMP added 1 h after T cell activation could still prevent cell death. In addition, the increased binding of AP-1, NF-AT, and NF-kappaB duri ng T cell activation was not significantly affected by cAMP. The prese nce of the inhibitory cAMP-mediated signals, together with the glucoco rticoid-induced pathway, suggest there are at least two distinct mecha nisms regulating AICD in immature lymphocytes.