title: c-Myc-induced transcription factor AP4 is required for host protection mediated by CD8+ T cells.
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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Chun
authors.identifier: 0000000171474236
authors.initials: C
authors.lastname: Chou
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Amelia K
authors.initials: AK
authors.lastname: Pinto
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Curtis
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Persaud
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Chih-Chung
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Edelson
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Allen
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Pearce
authors.affiliation: 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.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Egawa
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology
chemical_list: C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; C562117:transcription factor AP4, mouse