Pre-TCR signaling regulates IL-7 receptor alpha expression promoting thymocyte survival at the transition from the double-negative to double-positive stage.
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.
Trigueros
Cesar
C
Laboratory of Lymphocyte Molecular Biology, Cancer Research UK, London, England, UK.
Hozumi
Katsuto
K
Silva-Santos
Bruno
B
Bruno
Ludovica
L
Hayday
Adrian C
AC
Owen
Michael J
MJ
Pennington
Daniel J
DJ
D000818:Animals; D000906:Antibodies / Q000276:immunology; D017252:CD3 Complex; D016923:Cell Death / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D013950:Thymus Gland / Q000502:physiology*
D000906:Antibodies; D017252:CD3 Complex; C115335:CD3E protein, human; D018398:Homeodomain Proteins; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; C064658:RAG-1 protein