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: ジャーナルへの寄稿記事

47 引用 (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.

元の言語英語
ページ(範囲)1379-1387
ページ数9
ジャーナルGastroenterology
125
発行部数5
DOI
出版物ステータス出版済み - 1 1 2003

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Biliary Liver Cirrhosis
Clone Cells
T-Lymphocytes
Epithelial Cells
Autoantigens
Peripheral Tolerance
Antigen-Presenting Cells
Pyruvic Acid
Autoimmunity
Autoimmune Diseases
Oxidoreductases

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

これを引用

Distinct Costimulation Dependent and Independent Autoreactive T-Cell Clones in Primary Biliary Cirrhosis. / Kamihira, Takashi; Shimoda, Shinji; Harada, Kenichi; Kawano, Akira; Handa, Mizuki; Baba, Eishi; Tsuneyama, Koichi; Nakamura, Minoru; Ishibashi, Hiromi; Nakanuma, Yasuni; Gershwin, M. Eric; Harada, Mine.

:: Gastroenterology, 巻 125, 番号 5, 01.01.2003, p. 1379-1387.

研究成果: ジャーナルへの寄稿記事

Kamihira, T, Shimoda, S, Harada, K, Kawano, A, Handa, M, Baba, E, Tsuneyama, K, Nakamura, M, Ishibashi, H, Nakanuma, Y, Gershwin, ME & Harada, M 2003, 'Distinct Costimulation Dependent and Independent Autoreactive T-Cell Clones in Primary Biliary Cirrhosis', Gastroenterology, 巻. 125, 番号 5, pp. 1379-1387. https://doi.org/10.1016/j.gastro.2003.07.013
Kamihira, Takashi ; Shimoda, Shinji ; Harada, Kenichi ; Kawano, Akira ; Handa, Mizuki ; Baba, Eishi ; Tsuneyama, Koichi ; Nakamura, Minoru ; Ishibashi, Hiromi ; Nakanuma, Yasuni ; Gershwin, M. Eric ; Harada, Mine. / Distinct Costimulation Dependent and Independent Autoreactive T-Cell Clones in Primary Biliary Cirrhosis. :: Gastroenterology. 2003 ; 巻 125, 番号 5. pp. 1379-1387.
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abstract = "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.",
author = "Takashi Kamihira and Shinji Shimoda and Kenichi Harada and Akira Kawano and Mizuki Handa and Eishi Baba and Koichi Tsuneyama and Minoru Nakamura and Hiromi Ishibashi and Yasuni Nakanuma and Gershwin, {M. Eric} and Mine Harada",
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T1 - Distinct Costimulation Dependent and Independent Autoreactive T-Cell Clones in Primary Biliary Cirrhosis

AU - Kamihira, Takashi

AU - Shimoda, Shinji

AU - Harada, Kenichi

AU - Kawano, Akira

AU - Handa, Mizuki

AU - Baba, Eishi

AU - Tsuneyama, Koichi

AU - Nakamura, Minoru

AU - Ishibashi, Hiromi

AU - Nakanuma, Yasuni

AU - Gershwin, M. Eric

AU - Harada, Mine

PY - 2003/1/1

Y1 - 2003/1/1

N2 - 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.

AB - 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.

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