BLOCKED SIGNAL-TRANSDUCTION TO THE ERK AND JNK PROTEIN-KINASES IN ANERGIC CD4(-CELLS() T)

T cells activated by antigen receptor stimulation in the absence of ac cessory cell-derived costimulatory signals lose the capacity to synthe size the growth factor interleukin-2 (IL-2), a state called clonal ane rgy. An analysis of CD3- and CD28-induced signal transduction revealed reduced ERK and JNK enzyme activities in murine anergic T cells. The amounts of ERK and JNK proteins were unchanged, and the kinases could be fully activated in the presence of phorbol 12-myristrate 13-acetate . Dephosphorylation of the calcineurin substrate NFATp (preexisting nu clear factor of activated T cells) also remained inducible. These resu lts suggest that a specific block in the activation of ERK and JNK con tributes to defective IL-2 production in clonal anergy.