The role of MKK4 in T-cell development and immunity to viral infections.

The stress-activated protein kinases (SAPKs)/c-Jun-N-terminal-kinases (JNK) are members of the mitogen-activated protein kinase family. These kinases are responsible for transducing cellular signals through a phosphorylation-dependent signaling cascade. JNK activation in immune cells can lead to a range of critical cellular responses that include proliferation, differentiation and apoptosis. MKK4 is a SAPK that can activate both JNK1 and JNK2; however, its role in T-cell development and function has been controversial. Additionally, loss of either JNK1 or JNK2 has opposing effects in the generation of T-cell immunity to viral infection and cancer. We used mice with a conditional loss of MKK4 in T cells to investigate the in vivo role of MKK4 in T-cell development and function during lymphocytic choriomeningitis virus (LCMV) infection. We found no physiologically relevant differences in T-cell responses or immunity to either acute or chronic LCMV in the absence of MKK4.