Cellular size as a means of tracking mTOR activity and cell fate of CD4+ T cells upon antigen recognition.
Cellular size as a means of tracking mTOR activity and cell fate of CD4+ T cells upon antigen recognition.
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DOI：
10.1371/journal.pone.0121710
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Powell JD
中科院分区：
文献类型：
--
作者：
Pollizzi KN;Waickman AT;Patel CH;Sun IH;Powell JD
mTOR是代谢和免疫刺激的中心整合体，决定免疫细胞的激活、增殖和分化。在这项研究中，我们证明了在活化T细胞的克隆群体中，存在mTORhi和mTORlo细胞，它们表现出高度不同的代谢和免疫功能。通过利用mTOR激活控制细胞大小的作用，我们证明在抗原识别后，mTORhi CD4+ T细胞注定成为高度糖酵解效应细胞。相反，mTORlo T细胞优先发育成表达高水平Bcl-2、CD25和CD62L的长寿细胞。此外，mTORlo T细胞更倾向于分化为抑制性Foxp3+ T调节细胞，这种模式也在人类CD4+ T细胞中观察到。总的来说，这些研究为从naïve前体追踪效应T细胞和记忆T细胞的发展提供了机会，并促进了对告知这些命运的免疫和代谢程序的询问。
mTOR is a central integrator of metabolic and immunological stimuli, dictating immune cell activation, proliferation and differentiation. In this study, we demonstrate that within a clonal population of activated T cells, there exist both mTORhi and mTORlo cells exhibiting highly divergent metabolic and immunologic functions. By taking advantage of the role of mTOR activation in controlling cellular size, we demonstrate that upon antigen recognition, mTORhi CD4+ T cells are destined to become highly glycolytic effector cells. Conversely, mTORlo T cells preferentially develop into long-lived cells that express high levels of Bcl-2, CD25, and CD62L. Furthermore, mTORlo T cells have a greater propensity to differentiate into suppressive Foxp3+ T regulatory cells, and this paradigm was also observed in human CD4+ T cells. Overall, these studies provide the opportunity to track the development of effector and memory T cells from naïve precursors, as well as facilitate the interrogation of immunologic and metabolic programs that inform these fates.
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影响因子：
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