c-Myc-induced transcription factor AP4 is required for host protection mediated by CD8+ T cells

Nat Immunol. 2014 Sep;15(9):884-93. doi: 10.1038/ni.2943. Epub 2014 Jul 13.


Although the transcription factor c-Myc is essential for the establishment of 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 expression is downregulated. Here we identified AP4 as the transcription factor that was induced by c-Myc and sustained activation of antigen-specific CD8+ T cells. Despite normal priming, AP4-deficient CD8+ T cells failed to continue transcription of a broad range of c-Myc-dependent targets. Mice lacking AP4 specifically in CD8+ T cells showed enhanced susceptibility to infection with West Nile virus. Genome-wide analysis suggested that many activation-induced genes encoding molecules involved in metabolism were shared targets of c-Myc and AP4. Thus, AP4 maintains c-Myc-initiated cellular activation programs in CD8+ T cells to control microbial infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Lymphocyte Activation / immunology*
  • Mice
  • Proto-Oncogene Proteins c-myc / immunology*
  • Transcription Factors / immunology*
  • West Nile Fever / immunology


  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • transcription factor AP4, mouse