Laboratory for Transcriptional Regulation, Research Center for Allergy and Immunology, RIKEN, Suehiro-cho, Turumi-ku, Yokohama, Kanagawa, Japan.
Adv Immunol. 2011;110:71-110. doi: 10.1016/B978-0-12-387663-8.00003-X.
The helper versus cytotoxic-lineage choice of CD4(+)CD8(+) DP thymocytes correlates with MHC restriction of their T cell receptors and the termination of either CD8 or CD4 coreceptor expression. It has been hypothesized that transcription factors regulating the expression of the Cd4/Cd8 coreceptor genes must play a role in regulating the lineage decision of DP thymocytes. Indeed, progress made during the past decade led to the identification of several transcription factors that regulate CD4/CD8 expression that are as well important regulators of helper/cytotoxic cell fate choice. These studies provided insight into the molecular link between the regulation of coreceptor expression and lineage decision. However, studies initiated by the identification of ThPOK, a central transcription factor for helper T cell development, have offered another perspective on the cross-regulation between these two processes. Here, we review advances in our understanding of regulatory circuits composed of transcription factors and their link to epigenetic mechanisms, which play essential roles in specifying and sealing cell lineage identity during the CD4/CD8 commitment process of DP thymocytes.
CD4(+)CD8(+) DP 胸腺细胞的辅助细胞与细胞毒性谱系选择与 T 细胞受体的 MHC 限制以及 CD8 或 CD4 共受体表达的终止相关。人们假设调节 Cd4/Cd8 共受体基因表达的转录因子在调节 DP 胸腺细胞的谱系决定中发挥作用。事实上，在过去十年中取得的进展导致了几个调节 CD4/CD8 表达的转录因子的鉴定，这些转录因子也是辅助/细胞毒性细胞命运选择的重要调节剂。这些研究提供了对共受体表达调节和谱系决定之间分子联系的深入了解。然而，通过鉴定辅助 T 细胞发育的中央转录因子 ThPOK 而启动的研究为这两个过程之间的交叉调节提供了另一个视角。在这里，我们回顾了我们对由转录因子组成的调节回路及其与表观遗传机制的联系的理解的进展，这些机制在 DP 胸腺细胞的 CD4/CD8 决定过程中对特异性和密封细胞谱系身份发挥着至关重要的作用。
