Jones Mary Elizabeth, Zhuang Yuan
Department of Immunology, Duke University Medical Center, Box 3010, Durham, NC 27710, USA.
Immunity. 2007 Dec;27(6):860-70. doi: 10.1016/j.immuni.2007.10.014.
The T cell receptor (TCR) is required for positive selection and the subsequent transition from the CD4(+)CD8(+) double-positive (DP) to the CD4(+) or CD8(+) single-positive (SP) stage of alphabeta T cell development. The molecular mechanism that maintains DP 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 DP fate and to control the DP to SP transition. Simultaneous deletion of HEB and E2A in DP thymocytes was sufficient for DP 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 DP stage of development until a functional alphabetaTCR is produced.
T细胞受体（TCR）对于αβ T细胞发育过程中的阳性选择以及随后从CD4(+)CD8(+)双阳性（DP）阶段向CD4(+)或CD8(+)单阳性（SP）阶段的转变是必需的。在获得功能性TCR之前维持DP命运的分子机制尚不清楚。我们在此表明，结构和功能相关的转录因子HEB和E2A共同作用以维持DP命运并控制DP向SP的转变。DP胸腺细胞中HEB和E2A的同时缺失足以使DP向SP转变，且不依赖于TCR。HEB和E2A的缺失使DP细胞能够绕过TCR介导的阳性选择要求，下调与DP相关的基因，并上调SP特异性基因。这些结果确定HEB和E2A为守门人，它们将细胞维持在发育的DP阶段，直到产生功能性的αβ TCR。
