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Title

TGF-beta signaling of human T cells is modulated by the ancillary TGF-beta receptor endoglin

AuthorsSchmidt-Weber, C.B.; Letarte, Michelle; Kunzmann, D.; Ruckert, B.; Bernabéu, Carmelo ; Blaser, K.
Keywordscytokine receptor
Tlymphocytes
tolerance/suppression/anergy
Issue Date1-Jul-2005
PublisherOxford University Press
CitationInternational Immunology 17 921-930 (2005)
AbstractTransforming growth factor beta (TGF-β) inhibits T cell activation and alters differentiation of naive T cells into effector cells. Although four main cell-surface proteins can interact with TGF-β, only the signaling receptors type I (TGF-βR type I) and type II (TGF-βR 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-β-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-β, 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-β-mediated suppression
Description10 páginas, 6 figuras -- PAGS nros. 921-930
Publisher version (URL)http://dx.doi.org/ 0.1093/intimm/dxh272
URIhttp://hdl.handle.net/10261/49868
DOI10.1093/intimm/dxh272
ISSN0953-8178
E-ISSN1460-2377
Appears in Collections:(CIB) Artículos
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