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

Chun Chou, Amelia K. Pinto, Jonathan D. Curtis, Stephen P. Persaud, Marina Cella, Chih Chung Lin, Brian T. Edelson, Paul M. Allen, Marco Colonna, Erika L. Pearce, Michael S. Diamond, Takeshi Egawa

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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.

Original languageEnglish
Pages (from-to)884-893
Number of pages10
JournalNature immunology
Volume15
Issue number9
DOIs
StatePublished - Sep 2014

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