Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
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.
尽管转录因子 c-Myc 对于 T 细胞在初始化后建立代谢活跃和增殖状态至关重要，但它的表达是短暂的。目前尚不清楚 c-Myc 表达下调后，T 细胞激活是如何维持的。在这里，我们发现 AP4 是一种转录因子，它被 c-Myc 诱导，并持续激活抗原特异性 CD8+T 细胞。尽管初始化正常，但缺乏 AP4 的 CD8+T 细胞无法继续转录广泛的依赖于 c-Myc 的靶标。特异性缺乏 CD8+T 细胞中的 AP4 的小鼠对西尼罗河病毒感染的易感性增强。全基因组分析表明，许多参与代谢的激活诱导基因编码的分子是 c-Myc 和 AP4 的共同靶标。因此，AP4 维持 CD8+T 细胞中 c-Myc 启动的细胞激活程序，以控制微生物感染。
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