Pre-TCR signaling regulates IL7 receptor α expression promoting thymocyte survival at the transition from the double-negative to double-positive stage (original) (raw)

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-7Rα expression as developing thymocytes undergo β-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 β-selected cells. Thus, we identify a mechanism by which pre-TCR signaling controls the selective survival of TCRβ+ 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.