Promiscuous T cells selected by Escherichia coli: OGDC-E2 in primary biliary cirrhosis.
Promiscuous T cells selected by Escherichia coli: OGDC-E2 in primary biliary cirrhosis.
复制标题
由大肠杆菌选择的混杂 T 细胞：原发性胆汁性肝硬化中的 OGDC-E2。
DOI：
10.1016/s0896-8411(03)00024-6
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发表时间：
2003
影响因子：
12.8
通讯作者：
Harada,Mine
中科院分区：
文献类型：
--
作者：
Tanimoto,Hironori;Shimoda,Shinji;Nakamura,Minoru;Ishibashi,Hiromi;Kawano,Akira;Kamihira,Takashi;Matsushita,Sho;Gershwin,MEric;Harada,Mine
原发性胆汁性肝硬化（PBC）的病因仍然是个谜。一种引起关注的理论认为，PBC 是通过大肠杆菌的分子模拟诱导的。如果分子拟态是 PBC 中免疫原性反应的原因，那么大肠杆菌抗原特异性的 T 细胞克隆应该刺激人类免疫显性自身表位特异性的肽并与其发生交叉反应。为了解决这个问题，我们开发了针对大肠杆菌 OGDC-E2 肽的 T 细胞克隆。重要的是，我们证明了大肠杆菌 OGDC-E2 特异性 T 细胞克隆的存在，它们与人类线粒体等价物发生混杂反应。事实上，这种反应性的肝脏来源的 T 细胞前体频率显着增加，并且这种肝脏克隆仅在 PBC 患者中发现。总之，这些数据表明 PBC 是一种多重打击疾病，涉及遗传倾向、粘膜反应和混杂 T 细胞的激活；这种激活可以直接由细菌抗原发生，也可以通过化学修饰的细菌抗原间接发生。对相关机制的剖析不仅有助于了解 PBC 的免疫遗传学基础，而且可能有助于了解其致病病因。
The etiology of primary biliary cirrhosis (PBC) remains enigmatic. One theory that has attracted attention proposes that PBC is induced via molecular mimicry with Escherichia coli. If molecular mimicry is responsible for the immunogenic response in PBC, then T cell clones specific for E. coli antigens should stimulate and be cross-reactive with peptides specific for the human immunodominant autoepitopes. To address this issue, we developed T cell clones specific for E. coli OGDC-E2 peptide. Importantly, we demonstrate the presence of T cell clones specific for E. coli OGDC-E2 that react promiscuously with the human mitochondrial equivalents. Indeed, there was a significant increase in the liver derived T cell precursor frequency of such reactivity and such liver clones were only found in patients with PBC. In conclusion, these data suggest that PBC is a multi-hit disease involving a genetic predisposition, a mucosal response, and activation of promiscuous T cells; such activation may occur either directly from bacterial antigens, or indirectly through chemically-modified bacterial antigens. Dissection of the mechanisms involved will lead not only to understanding the immunogenetic basis of PBC, but likely its pathogenic etiology.