c-Myc-induced transcription factor AP4 is required for CD8(+) T cell-mediated host protection

Although c-Myc is essential to establish a metabolically active and proliferative state in T cells after priming, its expression is transient. It remains unknown how T cell activation is maintained after c-Myc down-regulation. Here, we identify AP4 as the transcription factor that is induced by c-Myc and sustains activation of antigen-specific CD8(+) T cells. Despite normal priming, AP4-deficient CD8(+) T cells fail to continue transcription of a broad range of c-Myc-dependent targets. Mice lacking AP4 specifically in CD8(+) T cells showed enhanced susceptibility to West Nile virus infection. Genome-wide analysis suggests that many activation-induced metabolic genes are shared targets of c-Myc and AP4. Thus, AP4 maintains c-Myc-initiated cellular activation programs in CD8(+) T cells to control microbial infections.