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A central role for Notch in effector CD8 + T cell differentiation

机译:Notch在效应CD8 + T细胞分化中的重要作用

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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.
机译:激活的CD8 + T细胞在末端效应细胞(TEC)或记忆前体细胞(MPC)命运之间进行选择。我们发现Notch信号传导受体控制着这种“选择”。 Notch促进了立即保护性TEC的分化,因此清除急性感染流感病毒需要使用Notch。 Notch激活了TEC特定基因表达程序的大部分,并抑制了MPC特定程序。炎性介质和白介素2(IL-2)通过依赖于代谢检查点激酶mTOR和转录因子T-bet的途径在幼稚CD8 + T细胞上诱导Notch的表达。这些途径随后在Notch的下游扩增,形成一个正反馈回路。因此,Notch充当中心枢纽,来自不同来源的信息汇聚在一起,以使效应T细胞分化与感染需求相匹配。

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