Peripheral tolerance and the qualitative characteristics of autoreactive T cell clones in primary biliary cirrhosis

Akira Kawano, Shinji Shimoda, Takashi Kamihira, Fumihiko Ishikawa, Hiroaki Niiro, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Minoru Nakamura, Atsumasa Komori, Kiyoshi Migita, Hiromi Ishibashi, Miyuki Azuma, M. Eric Gershwin, Mine Harada

研究成果: ジャーナルへの寄稿記事

11 引用 (Scopus)

抄録

Primary biliary cirrhosis is characterized by autoreactive T cells specific for the mitochondrial Ag PDC-E2163-176. We studied the ability of eight T cell clones (TCC) specific for PDC-E2163-176 to proliferate or become anergic in the presence of costimulation signals. TCC were stimulated with either human PDC-E2163-176, an Escherichia coli 2-oxoglutarate dehydrogenase mimic (OGDC-E234-47), or analogs with amino acid substitutions using HLA-matched allogeneic PBMC or mouse L-DR53 fibroblasts as APC. Based on their differential responses to these peptides (human PDC-E2 163-176, E. coli OGDC-E234-47) in the different APC systems, TCC were classified as costimulation dependent or independent. Only costimulation-dependent TCC could become anergic. TCC with costimulation- dependent responses to OGDC-E2 become anergic to PDC-E2 when preincubated with mimic, even if costimulation is independent for PDC-E2163-176. Anergic TCC produced IL-10. One selected TCC could not become anergic after preincubation with PDC-E2163-176-pulsed L-DR53 but became anergic using L-DR53 pulsed with PDC-E2 peptide analogs with a substitution at a critical TCR binding site. TCC that only respond to peptide-pulsed PBMC, but not L-DR53, proliferate with peptide-pulsed CD80/CD86-transfected L-DR53; however, anergy was not induced with peptide-pulsed L-DR53 transfected with only CD80 or CD86. These data highlight that costimulation plays a dominant role in maintaining peripheral tolerance to PBC-specific Ags. They further suggest that, under specific circumstances, molecular mimicry of an autoantigen may restore rather than break peripheral tolerance.

元の言語英語
ページ(範囲)3315-3324
ページ数10
ジャーナルJournal of Immunology
179
発行部数5
DOI
出版物ステータス出版済み - 9 1 2007

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Peripheral Tolerance
Biliary Liver Cirrhosis
Clone Cells
T-Lymphocytes
Peptides
dihydrolipoamide succinyltransferase
Ketoglutarate Dehydrogenase Complex
Escherichia coli
Molecular Mimicry
Autoantigens
Amino Acid Substitution
Interleukin-10
Fibroblasts
Binding Sites

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

これを引用

Peripheral tolerance and the qualitative characteristics of autoreactive T cell clones in primary biliary cirrhosis. / Kawano, Akira; Shimoda, Shinji; Kamihira, Takashi; Ishikawa, Fumihiko; Niiro, Hiroaki; Soejima, Yuji; Taketomi, Akinobu; Maehara, Yoshihiko; Nakamura, Minoru; Komori, Atsumasa; Migita, Kiyoshi; Ishibashi, Hiromi; Azuma, Miyuki; Gershwin, M. Eric; Harada, Mine.

:: Journal of Immunology, 巻 179, 番号 5, 01.09.2007, p. 3315-3324.

研究成果: ジャーナルへの寄稿記事

Kawano, A, Shimoda, S, Kamihira, T, Ishikawa, F, Niiro, H, Soejima, Y, Taketomi, A, Maehara, Y, Nakamura, M, Komori, A, Migita, K, Ishibashi, H, Azuma, M, Gershwin, ME & Harada, M 2007, 'Peripheral tolerance and the qualitative characteristics of autoreactive T cell clones in primary biliary cirrhosis', Journal of Immunology, 巻. 179, 番号 5, pp. 3315-3324. https://doi.org/10.4049/jimmunol.179.5.3315
Kawano, Akira ; Shimoda, Shinji ; Kamihira, Takashi ; Ishikawa, Fumihiko ; Niiro, Hiroaki ; Soejima, Yuji ; Taketomi, Akinobu ; Maehara, Yoshihiko ; Nakamura, Minoru ; Komori, Atsumasa ; Migita, Kiyoshi ; Ishibashi, Hiromi ; Azuma, Miyuki ; Gershwin, M. Eric ; Harada, Mine. / Peripheral tolerance and the qualitative characteristics of autoreactive T cell clones in primary biliary cirrhosis. :: Journal of Immunology. 2007 ; 巻 179, 番号 5. pp. 3315-3324.
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abstract = "Primary biliary cirrhosis is characterized by autoreactive T cells specific for the mitochondrial Ag PDC-E2163-176. We studied the ability of eight T cell clones (TCC) specific for PDC-E2163-176 to proliferate or become anergic in the presence of costimulation signals. TCC were stimulated with either human PDC-E2163-176, an Escherichia coli 2-oxoglutarate dehydrogenase mimic (OGDC-E234-47), or analogs with amino acid substitutions using HLA-matched allogeneic PBMC or mouse L-DR53 fibroblasts as APC. Based on their differential responses to these peptides (human PDC-E2 163-176, E. coli OGDC-E234-47) in the different APC systems, TCC were classified as costimulation dependent or independent. Only costimulation-dependent TCC could become anergic. TCC with costimulation- dependent responses to OGDC-E2 become anergic to PDC-E2 when preincubated with mimic, even if costimulation is independent for PDC-E2163-176. Anergic TCC produced IL-10. One selected TCC could not become anergic after preincubation with PDC-E2163-176-pulsed L-DR53 but became anergic using L-DR53 pulsed with PDC-E2 peptide analogs with a substitution at a critical TCR binding site. TCC that only respond to peptide-pulsed PBMC, but not L-DR53, proliferate with peptide-pulsed CD80/CD86-transfected L-DR53; however, anergy was not induced with peptide-pulsed L-DR53 transfected with only CD80 or CD86. These data highlight that costimulation plays a dominant role in maintaining peripheral tolerance to PBC-specific Ags. They further suggest that, under specific circumstances, molecular mimicry of an autoantigen may restore rather than break peripheral tolerance.",
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AU - Niiro, Hiroaki

AU - Soejima, Yuji

AU - Taketomi, Akinobu

AU - Maehara, Yoshihiko

AU - Nakamura, Minoru

AU - Komori, Atsumasa

AU - Migita, Kiyoshi

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AU - Gershwin, M. Eric

AU - Harada, Mine

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