Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells
Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells
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DOI：
10.4049/jimmunol.1301009
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发表时间：
2014-05-15
影响因子：
4.4
通讯作者：
Platsoucas, Chris D.
中科院分区：
文献类型：
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作者：
Lu, Song;White, John V.;Platsoucas, Chris D.
腹主动脉瘤（AAA）是一种常见的疾病，往往危及生命的后果。这种血管疾病占65岁或以上男性死亡人数的1-2%。自身免疫可能是AAA的发病机制之一。虽然有充分的证据表明浸润性T细胞基本上总是存在于AAA病变中，但对其在疾病的起始和/或进展中的作用知之甚少。为了确定浸润AAA病变的T细胞是否含有克隆扩增的T细胞群体，我们通过非回文衔接子PCR/V β特异性PCR和/或V β特异性PCR扩增β链TCR转录物，然后进行克隆和测序。我们在这篇文章中报告，10例AAA患者中有8例腹主动脉瘤样病变含有寡克隆T细胞群。在这些患者中鉴定出多个相同的b链TCR转录本拷贝。这些克隆扩增具有统计学显著性。这些结果表明，在AAA患者的瘤样病变浸润的ab TCR+ T淋巴细胞已经在瘤样病变部位体内经历了增殖和克隆扩增，以响应未鉴定的自身或非自身Ag。这一证据支持AAA是一种特异性Ag驱动的T细胞疾病的假设。
Abdominal aortic aneurysm (AAA) is a common disease with often life-threatening consequences. This vascular disorder is responsible for 1-2% of all deaths in men aged 65 years or older. Autoimmunity may be responsible for the pathogenesis of AAA. Although it is well documented that infiltrating T cells are essentially always present in AAA lesions, little is known about their role in the initiation and/or progression of the disease. To determine whether T cells infiltrating AAA lesions contain clonally expanded populations of T cells, we amplified beta-chain TCR transcripts by the nonpalindromic adaptor-PCR/V beta-specific PCR and/or V beta-specific PCR, followed by cloning and sequencing. We report in this article that aortic abdominal aneurysmal lesions from 8 of 10 patients with AAA contained oligoclonal populations of T cells. Multiple identical copies of b-chain TCR transcripts were identified in these patients. These clonal expansions are statistically significant. These results demonstrate that ab TCR+ T lymphocytes infiltrating aneurysmal lesions of patients with AAA have undergone proliferation and clonal expansion in vivo at the site of the aneurysmal lesion, in response to unidentified self-or nonself Ags. This evidence supports the hypothesis that AAA is a specific Ag-driven T cell disease.