Newly Generated CD4+ T Cells Acquire Metabolic Quiescence after Thymic Egress
Newly Generated CD4+ T Cells Acquire Metabolic Quiescence after Thymic Egress
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DOI：
10.4049/jimmunol.1700721
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发表时间：
2018-02
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通讯作者：
Shusong Zhang;Xinwei Zhang;Ke Wang;Xi Xu;Mingyang Li;Jun Zhang;Yan Zhang;Jie Hao;Xiu-yuan Sun;Yingyu Chen;Xiaohui Liu;Yingjun Chang;Rong Jin;Hounan Wu;Q. Ge
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作者：
Shusong Zhang;Xinwei Zhang;Ke Wang;Xi Xu;Mingyang Li;Jun Zhang;Yan Zhang;Jie Hao;Xiu-yuan Sun;Yingyu Chen;Xiaohui Liu;Yingjun Chang;Rong Jin;Hounan Wu;Q. Ge
成熟的幼稚T细胞以主动强制静止状态循环通过次级淋巴器官。当T细胞存在静止缺陷时，可以发现细胞存活和细胞功能受损。T细胞静止的关键特征之一是低基础代谢活性。目前尚不清楚T细胞在哪个发育阶段获得这种代谢静止。我们比较了胸腺中CD 4单阳性（SP）T细胞、CD 4+近期胸腺移出者（RTEs）和外周中成熟幼稚T细胞之间的线粒体。结果表明，与SP胸腺细胞相比，RTEs和幼稚T细胞具有减少的线粒体含量和线粒体活性氧。线粒体的这种下调需要T细胞从胸腺中排出，并且在年轻T细胞进入循环后早期发生。线粒体的自噬清除，而不是线粒体生物发生或分裂/融合，有助于RTE中的线粒体下调。增强的凋亡信号调节激酶1/MAPKs和减少雷帕霉素活性的RTEs相对于SP胸腺细胞的机制目标可能参与这种线粒体减少。这些结果表明，代谢静止期的获得是SP-RTE转换过程中重要的成熟过程之一。与功能成熟一起，它促进了年轻T细胞的存活和对激活刺激的完全反应。
Mature naive T cells circulate through the secondary lymphoid organs in an actively enforced quiescent state. Impaired cell survival and cell functions could be found when T cells have defects in quiescence. One of the key features of T cell quiescence is low basal metabolic activity. It remains unclear at which developmental stage T cells acquire this metabolic quiescence. We compared mitochondria among CD4 single-positive (SP) T cells in the thymus, CD4+ recent thymic emigrants (RTEs), and mature naive T cells in the periphery. The results demonstrate that RTEs and naive T cells had reduced mitochondrial content and mitochondrial reactive oxygen species when compared with SP thymocytes. This downregulation of mitochondria requires T cell egress from the thymus and occurs early after young T cells enter the circulation. Autophagic clearance of mitochondria, but not mitochondria biogenesis or fission/fusion, contributes to mitochondrial downregulation in RTEs. The enhanced apoptosis signal-regulating kinase 1/MAPKs and reduced mechanistic target of rapamycin activities in RTEs relative to SP thymocytes may be involved in this mitochondrial reduction. These results indicate that the gain of metabolic quiescence is one of the important maturation processes during SP–RTE transition. Together with functional maturation, it promotes the survival and full responsiveness to activating stimuli in young T cells.