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

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

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
2
Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
3
1] Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA. [2] Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA. [3] Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, USA.

Abstract

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.

PMID:
25029552
PMCID:
PMC4139462
DOI:
10.1038/ni.2943
[Indexed for MEDLINE]
Free PMC Article

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