Autoreactive T-Cell Responses in Primary Biliary Cirrhosis Are Proinflammatory Whereas Those of Controls Are Regulatory

Shinji Shimoda, Fumihiko Ishikawa, Takashi Kamihira, Atsumasa Komori, Hiroaki Niiro, Eishi Baba, Kenichi Harada, Kumiko Isse, Yasuni Nakanuma, Hiromi Ishibashi, M. Eric Gershwin, Mine Harada

研究成果: ジャーナルへの寄稿記事

51 引用 (Scopus)

抄録

Background & Aims: Autoreactive T cells that proliferate in response to autoantigens are found in both autoimmune disease and controls but have important qualitative differences in relative activation states, costimulation signal requirements, and pathogenetic significance. Understanding the mechanism for activation of autoreactive T cells will be critical in the treatment of autoimmune diseases. Methods: To understand the differences between autoreactive T cells in primary biliary cirrhosis (PBC) versus controls, we have developed autoreactive T-cell clones (TCCs) from patients with PBC and healthy controls and have used a peptide corresponding to the CD4 major autoepitope to define the relative proliferative and cytokine response. Results: Using an enzyme-linked immunosorbent spot assay, peripheral blood mononuclear cells (PBMCs) from PBC, but not from controls, produce interferon (IFN)-γ regardless of whether costimulation-competent or -incompetent antigen-presenting cells (APC) were used. In contrast, a significant number of IFN-γ-producing cells were found in PBMCs from controls but only if costimulation-competent PBMCs presented an autoantigenic peptide. In addition, costimulation-dependent autoreactive TCCs became anergic after a single round of stimulation in the presence of APC that did not provide a costimulatory signal, whereas some costimulation-independent autoreactive TCCs required repeated stimulation to become anergic and the others did not become anergic. Finally, anergic TCCs produced interleukin-10, but no IFN-γ, and exhibited regulatory functions in an antigen-dependent, cell contact-independent, and partially interleukin-10-mediated manner. Conclusions: These data relate specifically to the functional characteristics of autoreactive T cells in PBC but are also generically important for understanding the mechanisms for generating pathogenetic autoreactive T cells.

元の言語英語
ページ(範囲)606-618
ページ数13
ジャーナルGastroenterology
131
発行部数2
DOI
出版物ステータス出版済み - 1 1 2006

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Biliary Liver Cirrhosis
T-Lymphocytes
Clone Cells
Interferons
Blood Cells
Antigen-Presenting Cells
Interleukin-10
Autoimmune Diseases
Peptides
Enzyme-Linked Immunosorbent Assay
Cytokines
Antigens

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

これを引用

Autoreactive T-Cell Responses in Primary Biliary Cirrhosis Are Proinflammatory Whereas Those of Controls Are Regulatory. / Shimoda, Shinji; Ishikawa, Fumihiko; Kamihira, Takashi; Komori, Atsumasa; Niiro, Hiroaki; Baba, Eishi; Harada, Kenichi; Isse, Kumiko; Nakanuma, Yasuni; Ishibashi, Hiromi; Gershwin, M. Eric; Harada, Mine.

:: Gastroenterology, 巻 131, 番号 2, 01.01.2006, p. 606-618.

研究成果: ジャーナルへの寄稿記事

Shimoda, S, Ishikawa, F, Kamihira, T, Komori, A, Niiro, H, Baba, E, Harada, K, Isse, K, Nakanuma, Y, Ishibashi, H, Gershwin, ME & Harada, M 2006, 'Autoreactive T-Cell Responses in Primary Biliary Cirrhosis Are Proinflammatory Whereas Those of Controls Are Regulatory', Gastroenterology, 巻. 131, 番号 2, pp. 606-618. https://doi.org/10.1053/j.gastro.2006.05.056
Shimoda, Shinji ; Ishikawa, Fumihiko ; Kamihira, Takashi ; Komori, Atsumasa ; Niiro, Hiroaki ; Baba, Eishi ; Harada, Kenichi ; Isse, Kumiko ; Nakanuma, Yasuni ; Ishibashi, Hiromi ; Gershwin, M. Eric ; Harada, Mine. / Autoreactive T-Cell Responses in Primary Biliary Cirrhosis Are Proinflammatory Whereas Those of Controls Are Regulatory. :: Gastroenterology. 2006 ; 巻 131, 番号 2. pp. 606-618.
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abstract = "Background & Aims: Autoreactive T cells that proliferate in response to autoantigens are found in both autoimmune disease and controls but have important qualitative differences in relative activation states, costimulation signal requirements, and pathogenetic significance. Understanding the mechanism for activation of autoreactive T cells will be critical in the treatment of autoimmune diseases. Methods: To understand the differences between autoreactive T cells in primary biliary cirrhosis (PBC) versus controls, we have developed autoreactive T-cell clones (TCCs) from patients with PBC and healthy controls and have used a peptide corresponding to the CD4 major autoepitope to define the relative proliferative and cytokine response. Results: Using an enzyme-linked immunosorbent spot assay, peripheral blood mononuclear cells (PBMCs) from PBC, but not from controls, produce interferon (IFN)-γ regardless of whether costimulation-competent or -incompetent antigen-presenting cells (APC) were used. In contrast, a significant number of IFN-γ-producing cells were found in PBMCs from controls but only if costimulation-competent PBMCs presented an autoantigenic peptide. In addition, costimulation-dependent autoreactive TCCs became anergic after a single round of stimulation in the presence of APC that did not provide a costimulatory signal, whereas some costimulation-independent autoreactive TCCs required repeated stimulation to become anergic and the others did not become anergic. Finally, anergic TCCs produced interleukin-10, but no IFN-γ, and exhibited regulatory functions in an antigen-dependent, cell contact-independent, and partially interleukin-10-mediated manner. Conclusions: These data relate specifically to the functional characteristics of autoreactive T cells in PBC but are also generically important for understanding the mechanisms for generating pathogenetic autoreactive T cells.",
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T1 - Autoreactive T-Cell Responses in Primary Biliary Cirrhosis Are Proinflammatory Whereas Those of Controls Are Regulatory

AU - Shimoda, Shinji

AU - Ishikawa, Fumihiko

AU - Kamihira, Takashi

AU - Komori, Atsumasa

AU - Niiro, Hiroaki

AU - Baba, Eishi

AU - Harada, Kenichi

AU - Isse, Kumiko

AU - Nakanuma, Yasuni

AU - Ishibashi, Hiromi

AU - Gershwin, M. Eric

AU - Harada, Mine

PY - 2006/1/1

Y1 - 2006/1/1

N2 - Background & Aims: Autoreactive T cells that proliferate in response to autoantigens are found in both autoimmune disease and controls but have important qualitative differences in relative activation states, costimulation signal requirements, and pathogenetic significance. Understanding the mechanism for activation of autoreactive T cells will be critical in the treatment of autoimmune diseases. Methods: To understand the differences between autoreactive T cells in primary biliary cirrhosis (PBC) versus controls, we have developed autoreactive T-cell clones (TCCs) from patients with PBC and healthy controls and have used a peptide corresponding to the CD4 major autoepitope to define the relative proliferative and cytokine response. Results: Using an enzyme-linked immunosorbent spot assay, peripheral blood mononuclear cells (PBMCs) from PBC, but not from controls, produce interferon (IFN)-γ regardless of whether costimulation-competent or -incompetent antigen-presenting cells (APC) were used. In contrast, a significant number of IFN-γ-producing cells were found in PBMCs from controls but only if costimulation-competent PBMCs presented an autoantigenic peptide. In addition, costimulation-dependent autoreactive TCCs became anergic after a single round of stimulation in the presence of APC that did not provide a costimulatory signal, whereas some costimulation-independent autoreactive TCCs required repeated stimulation to become anergic and the others did not become anergic. Finally, anergic TCCs produced interleukin-10, but no IFN-γ, and exhibited regulatory functions in an antigen-dependent, cell contact-independent, and partially interleukin-10-mediated manner. Conclusions: These data relate specifically to the functional characteristics of autoreactive T cells in PBC but are also generically important for understanding the mechanisms for generating pathogenetic autoreactive T cells.

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