Pre-TCR signaling regulates IL-7 receptor α expression promoting thymocyte survival at the transition from the double-negative to double-positive stage
✍ Scribed by Cesar Trigueros; Katsuto Hozumi; Bruno Silva-Santos; Ludovica Bruno; Adrian C. Hayday; Michael J. Owen; Daniel J. Pennington
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 290 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
The pre-T cell receptor (pre-TCR) and IL-7 receptor (IL-7R) are critical mediators of survival, proliferation and differentiation in immature thymocytes. Here we show that pre-TCR signaling directly maintains IL-7Ralpha expression as developing thymocytes undergo beta-selection. Inhibition of IL-7/IL-7R signaling in (CD44-CD25-) DN4 cells results in decreased generation of double-positive thymocytes due to increased death of rapidly proliferating beta-selected cells. Thus, we identify a mechanism by which pre-TCR signaling controls the selective survival of TCRbeta+ thymocytes, and define a further stage of T cell differentiation in which signaling from a TCR regulates the ability of that cell to respond to cytokine.