| First Author | Tussiwand R | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 11 | Pages | 3371-80 |
| PubMed ID | 21882187 | Mgi Jnum | J:179517 |
| Mgi Id | MGI:5302599 | Doi | 10.1002/eji.201141824 |
| Citation | Tussiwand R, et al. (2011) The preTCR-dependent DN3 to DP transition requires Notch signaling, is improved by CXCL12 signaling and is inhibited by IL-7 signaling. Eur J Immunol 41(11):3371-80 |
| abstractText | The requirement for Notch signaling during T-cell development has been extensively studied. Nevertheless, the developmental stage at which it is required and whether additional signaling pathways are needed are still poorly understood. By using a stromal-cell-free culture system, we show that sorted double-negative 3 (DN3) thymocytes only require a Delta-like-4-induced Notch signal to differentiate into double-positive (DP) cells. This differentiation process is preTCR-alpha dependent. DN3 cells undergo 4-5 proliferation cycles, and the addition of the chemokine CXCL12 improves proliferation. IL-7 blocks the differentiation of DN3 cells to DP cells but not the Notch-induced proliferation of cultured DN3 cells. The impaired differentiation correlates with an inhibition of Rag-2 up-regulation. Overall, the in vitro stromal-cell-free culture system presented here also provides a powerful and unique tool for studying the mechanisms involved in the positive and negative selection of T cells. |
