HSP60 as a Target of Anti-Ergotypic Regulatory T Cells
HSP60 as a Target of Anti-Ergotypic Regulatory T Cells
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DOI：
10.1371/journal.pone.0004026
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发表时间：
2008-12-24
期刊：
影响因子：
3.7
通讯作者：
Cohen, Irun R.
中科院分区：
文献类型：
--
作者：
Quintana, Francisco J.;Mimran, Avishai;Cohen, Irun R.
据报道，60 kDa热休克蛋白（HSP60）以两种方式影响t细胞反应：作为toll样受体2信号的配体和作为抗原。在这里，我们描述了一种新的T细胞免疫调控HSP60的机制：HSP60被激活的T细胞（HSP60是一个麦角型）上调并呈现给调节性（抗麦角型）T细胞。经活化的T细胞呈递的HSP60是mhc限制性的，依赖于辅助分子CD28、CD80和CD86。抗自噬型T细胞通过增殖反应T细胞HSP60，并分泌IFN γ和TGF β 1。在体外，抗ergotypi T细胞通过其活化的T细胞靶标抑制IFN γ的产生。在体内，过继性转移抗ergotypic hsp60特异性T细胞系导致关节炎性T细胞分泌IFN γ减少，并改善佐剂性关节炎（AA）。因此，活化的T细胞呈递HSP60使它们成为HSP60特异性抗人血型调节性T细胞的靶标。然而，抗自噬型T调节因子（抗hsp60）与活化T细胞之间的直接相互作用也下调了调节因子。因此，通过作为麦角体的功能，HSP60可以控制效应T细胞和控制它们的调节性HSP60特异性T细胞。
The 60 kDa heat shock protein (HSP60) has been reported to influence T-cell responses in two ways: as a ligand of toll-like receptor 2 signalling and as an antigen. Here we describe a new mechanism of T-cell immuno-regulation focused on HSP60: HSP60 is up-regulated and presented by activated T cells ( HSP60 is an ergotope) to regulatory (anti-ergotypic) T cells. Presentation of HSP60 by activated T cells was found to be MHC-restricted and dependent on accessory molecules - CD28, CD80 and CD86. Anti-ergotypic T cells responded to T-cell HSP60 by proliferation and secreted IFN gamma and TGF beta 1. In vitro, the anti-ergotypic T cells inhibited IFN gamma production by their activated T-cell targets. In vivo, adoptive transfer of an anti-ergotypic HSP60-specific T-cell line led to decreased secretion of IFN gamma by arthritogenic T cells and ameliorated adjuvant arthritis ( AA). Thus, the presentation of HSP60 by activated T cells turns them into targets for anti-ergotypic regulatory T cells specific for HSP60. However, the direct interaction between the anti-ergotypic T regulators (anti-HSP60) and the activated T cells also down-regulated the regulators. Thus, by functioning as an ergotope, HSP60 can control both the effector T cells and the regulatory HSP60-specific T cells that control them.