Distinct Costimulation Dependent and Independent Autoreactive T-Cell Clones in Primary Biliary Cirrhosis

Takashi Kamihira, Shinji Shimoda, Kenichi Harada, Akira Kawano, Mizuki Handa, Eishi Baba, Koichi Tsuneyama, Minoru Nakamura, Hiromi Ishibashi, Yasuni Nakanuma, M. Eric Gershwin, Mine Harada

研究成果: Contribution to journalArticle査読

48 被引用数 (Scopus)

抄録

Background & Aims: Previous work has suggested that CD4+ CD28- or costimulation-independent T cells are increased in autoimmune diseases. In this study, we compared frequency and qualitative characteristics of autoreactive costimulation-independent or CD4+ CD28- T cells in primary biliary cirrhosis (PBC) by taking advantage of the well-defined immunodominant autoepitope of the E2 component of pyruvate dehydrogenase (PDC-E2). Methods: We determined the frequency of costimulation-independent autoreactive T cells that respond to PDC-E2 163-176 and the frequency of CD4+ CD28- T cells. Finally, we determined the role of biliary epithelial cells (BEC) as both an antigen-presenting cell or, alternatively, as a target cell for T-cell-mediated cytotoxicity. Results: The precursor frequency of costimulation-independent CD4+ T cells that respond to PDC-E2 163-176 and the frequency of CD4+ CD28- T cells were dramatically elevated in PBC. Furthermore, 2 types of T-cell clones that respond to PDC-E2 163-176 emerged from this study. One type was costimulation dependent and the other costimulation independent. Both types of clones lyse BEC in a similar effector target (E/T) ratio distribution. However, BEC did not help the proliferation of any T-cell clones. Furthermore, costimulation-independent T-cell clones do not become anergic by BEC. Conclusions: In PBC, costimulation-independent autoreactive T cells, which do not become anergic, increase and maintain the autoimmune response. In controls, although autoantigens are expressed on BEC and autoantigen-reactive T cells exist around BEC, autoantigen-reactive T cells are costimulation dependent and will become anergic and maintain peripheral tolerance.

本文言語英語
ページ(範囲)1379-1387
ページ数9
ジャーナルGastroenterology
125
5
DOI
出版ステータス出版済み - 11 2003

All Science Journal Classification (ASJC) codes

  • 肝臓学
  • 消化器病学

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