Pre-TCR signaling regulates IL-7 receptor alpha expression promoting thymocyte survival at the transition from the double-negative to double-positive stage

Eur J Immunol. 2003 Jul;33(7):1968-77. doi: 10.1002/eji.200323831.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • CD3 Complex*
  • Cell Death / physiology
  • Cell Division / physiology
  • Cell Survival
  • Gene Expression Regulation / physiology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mice
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Interleukin-7 / biosynthesis
  • Receptors, Interleukin-7 / genetics*
  • Signal Transduction / physiology
  • Thymus Gland / physiology*


  • Antibodies
  • CD3 Complex
  • CD3E protein, human
  • Homeodomain Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain
  • RAG-1 protein