Acquisition of a functional T cell receptor during T lymphocyte development is enforced by HEB and E2A transcription factors
Acquisition of a functional T cell receptor during T lymphocyte development is enforced by HEB and E2A transcription factors
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DOI：
10.1016/j.immuni.2007.10.014
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发表时间：
2007-12-01
期刊：
影响因子：
32.4
通讯作者：
Zhuang, Yuan
中科院分区：
文献类型：
--
作者：
Jones, Mary Elizabeth;Zhuang, Yuan
T细胞受体（TCR）是α - β T细胞发育的阳性选择和随后从CD4(+)CD8（+）双阳性（DIP）过渡到CD4（+）或CD8（+）单阳性（SP）阶段所必需的。在获得功能性TCR之前维持DID命运的分子机制尚不清楚。我们在这里表明，结构和功能相关的转录因子HEB和E2A共同维持DID命运并控制DID向SP的转变。DIP胸腺细胞中HEB和E2A的同时缺失足以使DIP独立于TCR向SP过渡。HEB和E2A的缺失允许DP细胞绕过tcr介导的阳性选择，下调DP相关基因，上调sp特异性基因。这些结果确定HEB和E2A是维持细胞在DID发育阶段直到产生功能性α - β TCR的看门人。
The T cell receptor (TCR) is required for positive selection and the subsequent transition from the CD4(+)CD8(+) double-positive (DIP) to the CD4(+) or CD8(+) single-positive (SP) stage of alpha beta T cell development. The molecular mechanism that maintains DID fate prior to the acquisition of a functional TCR is not clear. We have shown here that the structurally and functionally related transcription factors HEB and E2A work together to maintain DID fate and to control the DID to SP transition. Simultaneous deletion of HEB and E2A in DIP thymocytes was sufficient for DIP to SP transition independent of TCR. Loss of HEB and E2A allowed DP cells to bypass the requirement for TCR-mediated positive selection, downregulate DP-associated genes, and upregulate SP-specific genes. These results identify HEB and E2A as the gatekeepers that maintain cells at the DID stage of development until a functional alpha beta TCR is produced.