International Immunology Advance Access originally published online on June 20, 2005
International Immunology 2005 17(7):921-930; doi:10.1093/intimm/dxh272
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TGF-ß signaling of human T cells is modulated by the ancillary TGF-ß receptor endoglin
1 Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, CH-7270 Davos, Switzerland
2 Hospital for Sick Children and Department of Immunology, University of Toronto, 555 University Avenue, Toronto M5G1X8, Canada
3 Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, 28040 Madrid, Spain
Correspondence to: C. B. Schmidt-Weber; E-mail: csweber{at}siaf.unizh.ch
Transforming growth factor beta (TGF-ß) inhibits T cell activation and alters differentiation of naive T cells into effector cells. Although four main cell-surface proteins can interact with TGF-ß, only the signaling receptors type I (TGF-ßR type I) and type II (TGF-ßR type II) have so far been described on T cells. The aim of the present study was to investigate the expression of the ancillary receptor endoglin (CD105) by T cells and its role in TGF-ß-mediated signal transduction and function. CD105 expression was analyzed on resting and activated human CD4+ T cells by flow cytometry, western blot, immunoprecipitation, proliferation and SMAD-responsive reporter gene assays. CD4+ T cells constitutively expressed CD105 in memory T cells and partially also in naive T cells; however, surface expression is regulated and is increased following TCR engagement, which induced serine/threonine phosphorylation of CD105. In contrast to the suppressive signal mediated by the TGF-ß, cross-linking of CD105 substantially enhanced T cell proliferation, indicating that CD105 by itself mediates signal transduction. Furthermore, CD105 cross-linking induced SMAD-independent signaling via ERK kinase phosphorylation. The present study demonstrates that CD105 is expressed on the surface by activated CD4+ T cells and CD3 regulated by post-translational means. Furthermore, CD105 acts as a regulatory receptor, counteracting TGF-ß-mediated suppression.
Keywords: cytokine receptor, T lymphocytes, tolerance/suppression/anergy
Transmitting editor: S. Kaufmann
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