| First Author | Wojciechowski J | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 9 | Pages | 5717-26 |
| PubMed ID | 17442955 | Mgi Jnum | J:129570 |
| Mgi Id | MGI:3769701 | Doi | 10.4049/jimmunol.178.9.5717 |
| Citation | Wojciechowski J, et al. (2007) E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression. J Immunol 178(9):5717-26 |
| abstractText | Thymocytes undergoing TCRbeta 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 TCRbeta-chain and the Pre-Talpha-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-Talpha 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. |
