CXCR4 acts as a costimulator during thymic Β-selection

Paul C. Trampont, Annie Carole Tosello-Trampont, Yuelei Shen, Amanda K. Duley, Ann E. Sutherland, Timothy P. Bender, Dan R. Littman, Kodi S. Ravichandran

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

Passage through the Β-selection developmental checkpoint requires productive rearrangement of segments of the T cell antigen receptor-Β gene (Tcrb) and formation of a pre-TCR on the surface of CD4 CD 8 thymocytes. How other receptors influence ΒΒ-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 Β-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 Β-selection.

Original languageEnglish
Pages (from-to)162-170
Number of pages9
JournalNature immunology
Volume11
Issue number2
DOIs
StatePublished - Feb 2010

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