The c-Jun NH2-terminal kinase (JNK) signaling pathway has been implicated i
n the immune response that is mediated by the activation and differentiatio
n of CD4 helper T (T-H) cells into T(H)1 and T(H)2 effector cells. JNK acti
vity observed in wild-type activated T-H cells was severely reduced in T-H
cells from Jnk1(-/-) mice. The Jnk1(-/-) T cells hyperproliferated, exhibit
ed decreased activation-induced cell death, and preferentially differentiat
ed to T(H)2 cells. The enhanced production of T(H)2 cytokines by Jnk1(-/-)
cells was associated with increased nuclear accumulation of the transcripti
on factor NFATc. Thus, the JNK1 signaling pathway plays a key role in T cel
l receptor-initiated T-H cell proliferation, apoptosis, and differentiation
.