Schmidt-Weber Carsten B, Letarte Michelle, Kunzmann Steffen, Rückert Beate, Bernabéu Carmelo, Blaser Kurt
Swiss Institute of Allergy and Asthma Research, Obere Strasse 22, CH-7270 Davos, Switzerland.
Int Immunol. 2005 Jul;17(7):921-30. doi: 10.1093/intimm/dxh272. Epub 2005 Jun 20.
Transforming growth factor beta (TGF-beta) inhibits T cell activation and alters differentiation of naive T cells into effector cells. Although four main cell-surface proteins can interact with TGF-beta, only the signaling receptors type I (TGF-betaR type I) and type II (TGF-betaR 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-beta-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-beta, 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-beta-mediated suppression.
转化生长因子β（TGF-β）可抑制T细胞活化，并改变初始T细胞向效应细胞的分化。尽管有四种主要的细胞表面蛋白可与TGF-β相互作用，但迄今为止，在T细胞上仅发现了I型信号受体（TGF-βR I型）和II型信号受体（TGF-βR II型）。本研究的目的是探究T细胞辅助受体内皮糖蛋白（CD105）的表达及其在TGF-β介导的信号转导和功能中的作用。通过流式细胞术、蛋白质免疫印迹法、免疫沉淀法、增殖实验以及SMAD反应性报告基因检测，对静息和活化的人CD4⁺ T细胞上的CD105表达进行了分析。CD4⁺ T细胞在记忆T细胞中组成性表达CD105，在部分初始T细胞中也有表达；然而，其表面表达受到调控，在TCR激活后会增加，这会诱导CD105的丝氨酸/苏氨酸磷酸化。与TGF-β介导的抑制信号相反，CD105的交联显著增强了T细胞增殖，表明CD105自身可介导信号转导。此外，CD105交联通过ERK激酶磷酸化诱导非SMAD信号通路。本研究表明，活化的CD4⁺ T细胞表面通过翻译后修饰方式表达CD105和CD3。此外，CD105作为一种调节性受体，可抵消TGF-β介导的抑制作用。
