1] Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands. [2] Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
Nat Immunol. 2014 Dec;15(12):1143-51. doi: 10.1038/ni.3027. Epub 2014 Oct 26.
Activated CD8(+) T cells choose between terminal effector cell (TEC) or memory precursor cell (MPC) fates. We found that the signaling receptor Notch controls this 'choice'. Notch promoted the differentiation of immediately protective TECs and was correspondingly required for the clearance of acute infection with influenza virus. Notch activated a major portion of the TEC-specific gene-expression program and suppressed the MPC-specific program. Expression of Notch was induced on naive CD8(+) T cells by inflammatory mediators and interleukin 2 (IL-2) via pathways dependent on the metabolic checkpoint kinase mTOR and the transcription factor T-bet. These pathways were subsequently amplified downstream of Notch, creating a positive feedback loop. Notch thus functions as a central hub where information from different sources converges to match effector T cell differentiation to the demands of an infection.
激活的 CD8(+) T 细胞在终末效应细胞 (TEC) 和记忆前体细胞 (MPC) 命运之间做出选择。我们发现信号受体 Notch 控制着这种“选择”。Notch 促进了具有即刻保护作用的 TEC 的分化，并且相应地对于清除流感病毒的急性感染是必需的。Notch 激活了大部分 TEC 特异性基因表达程序，并抑制了 MPC 特异性程序。炎性介质和白细胞介素 2 (IL-2) 通过依赖于代谢检查点激酶 mTOR 和转录因子 T-bet 的途径诱导初始 CD8(+) T 细胞表达 Notch。这些途径随后在 Notch 下游被放大，形成正反馈环。因此，Notch 作为一个中央枢纽，不同来源的信息汇聚于此，将效应 T 细胞分化与感染的需求相匹配。
