Elevation of intracellular cyclic AMP induces an anergic-like state in Th1 clones.

Because elevated intracellular cAMP suppresses T cell receptor (TCR)-mediated effector activity and/or proliferation in response to antigen but does not always affect IL-2-stimulated proliferation, the effects of cAMP on a T lymphocyte response to antigen resemble antigen-induced anergy. To test the hypothesis that elevated cAMP induces anergy in T lymphocytes, we have precultured murine Th1 clones responsive to porcine myelin basic protein (PMBP) with dibutyryl cyclic AMP (dbcAMP) or forskolin and subsequently removed the dbcAMP or forskolin and measured the proliferative response of the clones to antigen and antigen-presenting cells (APC) in the presence or absence of exogenously added interleukin-2 (IL-2). Cells precultured with dbcAMP or forskolin for 3 days did not proliferate or produce IL-2 in response to antigen and APC, but did proliferate to antigen and APC in the presence of IL-2. Cells that had not been stimulated recently with antigen/APC or IL-2 were not affected by dbcAMP, while cells stimulated recently with antigen/APC and IL-2 were susceptible to the anergizing effect of dbcAMP. These observations support the hypothesis that elevation in intracellular cAMP in antigen-activated Th1 clones, prior to subsequent culture with antigen, induces a state of anergy.