Promiscuous T cells selected by Escherichia coli: OGDC-E2 in primary biliary cirrhosis

Hironori Tanimoto, Shinji Shimoda, Minoru Nakamura, Hiromi Ishibashi, Akira Kawano, Takashi Kamihira, Sho Matsushita, M. Eric Gershwin, Mine Harada

研究成果: ジャーナルへの寄稿学術誌査読

24 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)255-263
ページ数9
ジャーナルJournal of Autoimmunity
20
3
DOI
出版ステータス出版済み - 5月 2003

!!!All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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