Pre-TCR signaling regulates IL-7 receptor alpha expression promoting thymocyte survival at the transition from the double-negative to double-positive stage |
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Authors: | Trigueros Cesar Hozumi Katsuto Silva-Santos Bruno Bruno Ludovica Hayday Adrian C Owen Michael J Pennington Daniel J |
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Institution: | Laboratory of Lymphocyte Molecular Biology, Cancer Research UK, London, England, UK. |
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Abstract: | 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. |
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Keywords: | IL‐7 receptor Pre‐TCR Proliferation Survival |
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