c-Jun NH₂-terminal kinase (JNK)1 and jnk2 signaling pathways have divergent roles in CD8⁺ T cell-mediated antiviral immunity

c-Jun NH₂-terminal kinases (JNK) play important roles in T helper cell (Th) proliferation, differentiation, and maintenance of Th1/Th2 polarization. To determine whether JNKs are involved in antiviral T cell immunity, and whether JNK1 and JNK2 bear biological differences, we investigated the immune responses of JNK1-deficient and JNK2-deficient mice to lymphocytic choriomeningitis virus (LCMV). After LCMV infection, wild-type (JNK^+/+) mice had a 5- to 10-fold increase in splenic CD8⁺ T cells. In contrast, infected JNK1^-/- mice showed a significantly lower virus-specific CD8⁺ T cell expansion. However, JNK1^-/- mice cleared LCMV infection with similar kinetics as JNK^+/+ mice. Splenic T cells from LCMV-infected JNK1^-/- animals produced interferon γ after stimulation with viral peptides. However, fewer JNK1^-/- T cells acquired an activated phenotype (CD44^hi) and more JNK^1-/- CD8⁺ CD44^hi cells underwent apoptosis than JNK^+/+ cells at the peak of the primary response. In contrast, LCMV-infected JNK2^-/- mice generated more virus-specific CD8⁺ T cells than JNK^+/+ mice. These results indicate that JNK1 and JNK2 signal pathways have distinct roles in T cell responses during a viral infection. JNK1 is involved in survival of activated T cells during immune responses, and JNK2 plays a role in control of CD8⁺ T cell expansion in vivo.