The Wistar Institute, Philadelphia, Pennsylvania, USA.
Nat Immunol. 2011 Jun;12(6):544-50. doi: 10.1038/ni.2034. Epub 2011 May 1.
The molecular mechanisms that underlie T cell quiescence are poorly understood. Here we report that mature naive CD8(+) T cells lacking the transcription factor Foxp1 gained effector phenotype and function and proliferated directly in response to interleukin 7 (IL-7) in vitro. Foxp1 repressed expression of the IL-7 receptor α-chain (IL-7Rα) by antagonizing Foxo1 and negatively regulated signaling by the kinases MEK and Erk. Acute deletion of Foxp1 induced naive T cells to gain an effector phenotype and proliferate in lympho-replete mice. Foxp1-deficient naive CD8(+) T cells proliferated even in lymphopenic mice deficient in major histocompatibility complex class I. Our results demonstrate that Foxp1 exerts essential cell-intrinsic regulation of naive T cell quiescence, providing direct evidence that lymphocyte quiescence is achieved through actively maintained mechanisms that include transcriptional regulation.
T 细胞静止的分子机制尚未完全阐明。在这里，我们报告说，缺乏转录因子 Foxp1 的成熟幼稚 CD8(+) T 细胞获得了效应表型和功能，并可直接对白细胞介素 7(IL-7)作出反应而在体外增殖。Foxp1 通过拮抗 Foxo1 抑制 IL-7 受体 α 链(IL-7Rα)的表达，并负调控 MEK 和 Erk 激酶的信号转导。Foxp1 的急性缺失可诱导幼稚 T 细胞获得效应表型并在淋巴丰富的小鼠中增殖。即使在 MHC Ⅰ类主要组织相容性复合物缺陷的淋巴缺失小鼠中，Foxp1 缺陷的幼稚 CD8(+) T 细胞仍可增殖。我们的研究结果表明，Foxp1 对幼稚 T 细胞静止发挥了重要的细胞内调节作用，这为淋巴细胞静止是通过包括转录调控在内的主动维持机制来实现提供了直接证据。
