CXCR4 acts as a costimulator during thymic beta-selection.
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.
Trampont
Paul C
PC
Carter Immunology Center, University of Virginia, Charlottesville, Virginia, USA.
Tosello-Trampont
Annie-Carole
AC
Shen
Yuelei
Y
Duley
Amanda K
AK
Sutherland
Ann E
AE
Bender
Timothy P
TP
Littman
Dan R
DR
Ravichandran
Kodi S
KS
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
C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4