title: Pre-TCR signaling regulates IL-7 receptor alpha expression promoting thymocyte survival at the transition from the double-negative to double-positive stage.
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.
authors.affiliation: Laboratory of Lymphocyte Molecular Biology, Cancer Research UK, London, England, UK.
authors.forename: Cesar
authors.initials: C
authors.lastname: Trigueros
authors.forename: Katsuto
authors.initials: K
authors.lastname: Hozumi
authors.forename: Bruno
authors.initials: B
authors.lastname: Silva-Santos
authors.forename: Ludovica
authors.initials: L
authors.lastname: Bruno
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Hayday
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Pennington
mesh_terms: 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*
chemical_list: 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