期刊
JOURNAL OF IMMUNOLOGY
卷 178, 期 9, 页码 5717-5726出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.9.5717
关键词
-
类别
资金
- NCI NIH HHS [R01 CA072433-10, R01 CA072433-09, R01 CA072433] Funding Source: Medline
- NIGMS NIH HHS [R01 GM059638-07, R01 GM059638-06, R01 GM059638, R01 GM059638-08, R01 GM 059638, R01 GM059638-05] Funding Source: Medline
Thymocytes undergoing TCR beta gene rearrangements are maintained in a low or nonproliferating state during early T cell development. This block in cell cycle progression is not released until the expression of a functional pre-TCR, which is composed of a successfully rearranged TCR beta-chain and the Pre-Ta-chain. The regulatory molecules responsible for the coordination of these differentiation and proliferation events are currently unknown. E2A and HEB are structurally and functionally related basic helix-loop-helix transcription factors involved in T cell development. To reveal the function of E2A and HEB through the stage of pre-TCR expression and alleviate functional compensation between E2A and HEB, we use a double-conditional knockout model. The simultaneous deletion of E2A and HEB in developing thymocytes leads to a severe developmental block before pre-TCR expression and a dramatic reduction of Pre-Ta expression. These developmentally arrested thymocytes exhibit increased proliferation in vivo and dramatic expansion ex vivo in response to IL-7 signaling. These results suggest that E2A and HEB are not only critical for T cell differentiation but also necessary to retain developing thymocytes in cell cycle arrest before pre-TCR expression. The Journal of Immunology, 2007, 178: 5717-5726.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据