T-cells from advanced atherosclerotic lesions recognize hHSP60 and have a restricted T-cell receptor repertoire
T-cells from advanced atherosclerotic lesions recognize hHSP60 and have a restricted T-cell receptor repertoire
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DOI：
10.1016/j.exger.2007.11.009
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发表时间：
2008-03-01
影响因子：
3.9
通讯作者：
Wick, Georg
中科院分区：
文献类型：
--
作者：
Rossmann, Andrea;Henderson, Blair;Wick, Georg
动脉粥样硬化是一种多因素的慢性炎症性疾病，其根本原因尚不清楚。也有文献记载，t细胞是最早迁移到动脉内膜血管层的细胞之一，但它们在那里的功能仍然无法解释。临床和实验数据证明，动脉粥样硬化始于一种基于体液和细胞免疫的自身免疫反应，该反应是针对一种系统发育高度保守的应激蛋白——热休克蛋白60 （HSP60）。在本研究中，我们对颈动脉内膜切除标本中的t细胞进行了表型表征，并测试了它们对人HSP60的反应性。此外，通过免疫镜分析确定t细胞系的t细胞受体库。我们发现病灶内有CD4（+）和CD8（+）混合的t细胞群，CD8+细胞占轻微优势。ifn - γ的产生优于IL-4的产生。与外周t细胞相比，t细胞对人HSP60的反应在病灶内细胞中显著增加。与PBMC的多克隆模式相反，病变来源的t细胞显示出寡克隆限制的曲目。这些结果清楚地表明HSP60是一个主要的抗原候选者，并且在晚期人类动脉粥样硬化病变中发生了寡聚t细胞扩增。(c) 2008年Elsevier Inc.出版
Atherosclerosis is a multifactorial, chronic-inflammatory disease for which the underlying cause remains unknown. It is also well documented that T-cells are among the first cells to migrate into the arterial intimal vessel layer, but their function there is still unexplained. Clinical and experimental data have provided evidence that atherosclerosis starts as an autoimmune reaction based on humoral and cellular immunity against a phylogenetically highly conserved stress protein, heat shock protein 60 (HSP60). In the present study, we phenotypically characterized T-cells from endarterectomized specimens of the carotid artery, and tested their reactivity to human HSP60. In addition, the T-cell receptor repertoire of the T-cell lines was defined by immunoscope analysis. We found a mixed population of CD4(+) and CD8(+) intralesional T-cells, with a slight predominance of CD8+ cells. IFN-gamma production prevailed over IL-4 production. The T-cell reaction against human HSP60 was significantly increased in intralesional cells compared to peripheral T-cells. The lesion-derived T-cells showed an oligoclonally-restricted repertoire, in contrast to the polyclonal pattern of PBMC. These results clearly show that HSP60 is a major antigenic candidate, and that an oligocional T-cell expansion takes place in advanced human atherosclerotic lesions. (c) 2008 Published by Elsevier Inc.