CD28 signaling augments Elk-1-dependent transcription at the c-fos gene during antigen stimulation

Untransformed CD4(+) Th1 cells stimulated with Ag and APC demonstrated a de pendence on B7- and CD28-mediated costimulatory signals for the expression and function of A-P-1 proteins. The induction of transactivation by the c-f os gene regulator Elk-1 mirrored this requirement for TCR and CD28 signal i ntegration. c-jun N-terminal kinase (JNK) (but not extracellular signal-reg ulated kinase or p38) protein kinase activity was similarly inhibited by ne utralizing anti-B7 mAbs. Blockade of JNK protein kinase activity with SB 20 2190 prevented both Elk-1 transactivation and c-Fos induction. These result s identify a unique role for B7 costimulatory molecules and CD28 in the act ivation of JNK during Ag stimulation in Th1 cells, and suggest that JNK reg ulates Elk-1 transactivation at the c-fos gene to promote the formation of AP-1 complexes important to IL-2 gene, expression.