Costimulation by extracellular matrix proteins determines the response to TCR ligation
Costimulation by extracellular matrix proteins determines the response to TCR ligation
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DOI：
10.1006/cimm.2001.1800
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发表时间：
2001-05-25
影响因子：
4.3
通讯作者：
Weber, GF
中科院分区：
文献类型：
--
作者：
Adler, B;Ashkar, S;Weber, GF
尽管T细胞抗原受体（TCR）的连接对于T细胞的应答性和抗原特异性是重要的，但它不足以引起应答。为了确定是否需要共刺激反映了通过TCR的信号转导的强度不足或在没有共配体的情况下信号传导的绝对阻断，我们研究了在无血清条件下消除各种细胞外基质蛋白的共刺激的T细胞活化，否则这些蛋白具有无所不在和经常被忽视的作用。TCR的参与导致Fas的诱导，但不导致可测量的IL-2分泌或凋亡。这些激活参数是通过整合素α（v）β（3）的共刺激诱导的。此外，T细胞的存活或消除取决于与该辅助受体结合的配体的类型，其中玻连蛋白、纤连蛋白和纤维蛋白原有效地诱导细胞凋亡和IL-2产生，而骨桥蛋白和巢蛋白介导IL-2分泌而不引起程序性细胞死亡。与这些配体的细胞因子特性一致，差异共刺激依赖于它们以可溶性而不是固定化形式呈现。通过β 3-整合素的共连接确定活化T细胞的清除与存活可能与形成T细胞库的基本胸腺后机制有关。(C)北京：科学出版社.
Although ligation of the T-cell antigen receptor (TCR) is central to the responsiveness and antigen specificity of T-cells, it is insufficient to elicit a response. To determine whether the need for costimulation reflects inadequate strength of signal transduction through the TCR or an absolute block of signaling in the absence of a coligand, we studied T-cell activation under serum-free conditions eliminating costimulation by various extracellular matrix proteins which otherwise have an omnipresent and frequently overlooked effect. Engagement of the TCR leads to induction of Fas, but not to measurable IL-2 secretion or apoptosis. Those activation parameters are induced by costimulation through integrin alpha (v)beta (3). Furthermore, T-cell survival or elimination is determined by the type of ligand binding to this coreceptor with vitronectin, fibronectin, and fibrinogen efficiently inducing apoptosis and IL-2 production while osteopontin and entactin mediate IL-2 secretion comparably without causing programmed cell death. Consistent with the cytokine properties of these ligands, differential costimulation depends on their presentation in soluble rather than immobilized form. The determination of elimination versus survival of activated T-cells by coligation of beta (3)-integrins may have bearing on the fundamental postthymic mechanisms that shape the T-cell repertoire. (C) 2001 Academic Press.