title: CXCR4 acts as a costimulator during thymic beta-selection.
abstract: Passage through the beta-selection developmental checkpoint requires productive rearrangement of segments of the T cell antigen receptor-beta gene (Tcrb) and formation of a pre-TCR on the surface of CD4(-)CD8(-) thymocytes. How other receptors influence betabeta-selection is less well understood. Here we define a new role for the chemokine receptor CXCR4 during T cell development. CXCR4 functionally associated with the pre-TCR and influenced beta-selection by regulating the steady-state localization of immature thymocytes in thymic subregions, by facilitating optimal pre-TCR-induced survival signals, and by promoting thymocyte proliferation. We also characterize functionally relevant signaling molecules downstream of CXCR4 and the pre-TCR in thymocytes. Our data designate CXCR4 as a costimulator of the pre-TCR during beta-selection.
authors.affiliation: Carter Immunology Center, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Trampont
authors.forename: Annie-Carole
authors.initials: AC
authors.lastname: Tosello-Trampont
authors.forename: Yuelei
authors.initials: Y
authors.lastname: Shen
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Duley
authors.forename: Ann E
authors.initials: AE
authors.lastname: Sutherland
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Bender
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
authors.forename: Kodi S
authors.initials: KS
authors.lastname: Ravichandran
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D019674:Genes, T-Cell Receptor beta / Q000276:immunology; D047468:Immunoprecipitation; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D018613:Microscopy, Confocal; D019718:Receptors, CXCR4 / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4