The preTCR-dependent DN3 to DP transition requires Notch signaling, is improved by CXCL12 signaling and is inhibited by IL-7 signaling
✍ Scribed by Roxane Tussiwand; Corinne Engdahl; Nadine Gehre; Nabil Bosco; Rod Ceredig; Antonius G. Rolink
- Book ID
- 102166127
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 416 KB
- Volume
- 41
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
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‐α 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.