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Nat Immunol. 2010 Feb;11(2):162-70. doi: 10.1038/ni.1830. Epub 2009 Dec 13.

CXCR4 acts as a costimulator during thymic beta-selection.

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1
Carter Immunology Center, University of Virginia, Charlottesville, Virginia, USA.

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.

PMID:
20010845
PMCID:
PMC2808461
DOI:
10.1038/ni.1830
[Indexed for MEDLINE]
Free PMC Article
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