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Evidence against epitope spreading of T cells in autoimmune diseases.

Research Project

Project/Area Number 14370161
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionThe University of Tokyo

Principal Investigator

YAMAMOTO Kazuhiko  The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (80191394)

Co-Investigator(Kenkyū-buntansha) KOMAGATA Yoshinori  The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (60281995)
MISAKI Yoshiikata  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (60219615)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2003: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2002: ¥7,700,000 (Direct Cost: ¥7,700,000)
Keywordsautommune disease / epitope / T cells / T cell receptor / pathogenic T cell / T細胞クローン
Research Abstract

Epitope spreading is a well known phenomenon of autoimrnune process especially in the induction phase of the diseases. We examine whether this phenomenon is also working in the stage of advanced phase of autoimmune disorders. We have examined accumulated T cells clones in the several organs of spontaneous models of autoimmune disorders by RT PCR/SSCP analysis of T cell receptor. We found that there are extensive accumulations of T cells in the lesions of late phase animals and the same clones exist in the different pathological lesions of kidney, lung and central nervous system of such animals. We then constructed cDNA library from a single cell isolated from the lesions and obtained fill length cDNAs encoding alpha and beta chains of T cell receptor. After identification of the in vivo accumulated clones to the cloned T cell receptors, cytokine messages were examined using the cDNA library. Some clones were found to express interferon gamma message, suggesting that such clones were pathogenic T cells. We are now trying to reconstitute T cell receptor function by retroviral gene transfer in order to know the pathogenic properties of such clones.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Yamada R, Suzuki A, Chang X, Yamamoto K: "Peptidylarginine deiminase type 4: identification of a rheumatoid arthritis-susceptible gene."Trends Mol Med. 9. 503-508 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki K, Sawada T, Murakami A, Matsui T, Tohma S, Nakazono K, Yamamoto K. Etc.: "High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis."Scand J Rheumatol. 32. 197-204 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tokuhiro S. et al.: "An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis."Nature Genet.. 35. 341-348 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tahara H. et al.: "Reconstitution of CD8^+ T cells by retroviral transfer of the TCR αβ-chain genes isolated from a clonally expanded P815-infiltrating lymphocytes^1."J Immunol.. 171. 2154-2160 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki A. et al.: "Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis."Nature Genet.. 35. 395-402 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sekiya T, Tsunemi Y, Miyamasu M, Ohta K, Morita A, Saeki H, Yamamoto K, etc.: "Variations in the human Th2-specific chemokine TARC gene."Immunogenetics. 54. 742-745 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takami K, Takuwa N, Okazaki H, Kobayashi M, Yamamoto K, etc.: "Interferon-γ inhibits hepatocycyte growth factor-simulated cell proliferation of human bronchial epithelial cells upregulation of p27^<kip1> cyclin-dependent kinase inhibitor."AM J Respir Cell Mol Biol. 26. 231-238 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawahata K. et al.: "Generation of CD4+CD25+ regulatory Tcells from autoreactive Tcells simultaneously with their negative selection in the thymus and from nonautoreactive Tcells by endogeneous TCR expression."J Immunol.. 168. 4399-4405 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahama H, Masuko-hongo, K.Tanaka A, Kawa Y, Yamamoto K, etc.: "T-cell clonotypes specific for dermatophagoides pteronyssinus in the skin lesions of patients with atopic dermatitis."Human Immunol. 63. 558-566 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kono H, Suzuki T, Yamamoto K, etc.: "Spatial raft coalescence represents an initial step in FcγβR Signaling."J Immunnol. 169. 193-203 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawahata K. et al.: "Peripheral tolerance to a nuclear autoantigen : dendritic cells expressing a nuclear autoantigen lead to persistent anergic state of CD4+ autoreactive T cells after proliferation."J Immunol.. 168. 1103-1112 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada R, Suzuki A, Chang X, Yamamoto K.: "Peptidylarginine deiminase type4 : identification of a rheurnatoid arthritis-susceptible gene"Trends Mol Med. 9. 503-508 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki K, Sawada T, Mwrakarni A, Matsui T, Tohrna S, Nakazono K, Takemura M, Takasaki Y, Mimori T, Yamamoto K: "High diagnostic performance of ELISA detection of antibodies to citrufinated antigens in rheumatoid artkritis"Scand J Rlieumatol. 32. 197-2004 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tokuhin o S, Yamada R, Chang X, Suzuki A, Koch Y, Sawada T, Suzuki M, Nagasaki M, Ohtsuki M, Olio M, Furukawa H, Nagashima M, Yoshino S, Mabuchi A, Sekine A, Saito S, Takahashi A, Tunoda T, Nakamura Y, Yamamoto K.: "An intronic SNP in a RUNXI binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis"Nature Gene. 35. 341-348 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tahara H, Fujio K, Araki Y, Setoguchi K, Misalci Y, Kitamura T, Yamamoto K: "Reconstitution of CD8^+ T cells by retroviral transfer of the TCR αβ-chain genes isolated from a clonally expanded P815-infiltrating lymphocyte^1"J Immunol. 171. 2154-2160 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Thunoda T, Nakamura Y, Yamamoto K: "Functional haplotypes of PAD14, encoding citnullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis"Nature Genet. 34. 395-402 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sekiya T, Tsunemi Y, Miyamasu M, Ohta K, Morita A, Saeki H, Matsushima K, Yoshie O, Tuchiya N, Yamaguchi M, Yamamoto K, Tamaki K, Hirai K.: "Variations in the human Th2-specific chemokine TARC gene"Immunogenetics. 54. 742-745 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takanii K, Takuwa N, Okazaki H, Kobayashi M, Ohtoshi T, Kawasaki S, Dohi M, Yamamoto K, Nakamura T, Tanaka M, Nakahara K, Takuwa Y, Takizawa H.: "Interferon-γ inhibits hepatocyte growth factor-simulated cell proliferation of human bronchial epithelial cells upregulation of p27^<kip1> cyclin-dependent kinase inhibitor."Am J Respir Cell Mol Biol. 26. 231-238 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawahata K, Misaki Y, Yamauchi M, Tsunekawa S, Setoguchi K, Miyazaki J, Yamamoto K: "Generation of CD4+CD25+ regulatory Tcells from autoneactive Tcells simultaneously with their negative selection in the thymus and from nonautoreactive Tcells by endogeneous TCR expression"J.Immunol. 168. 4399-4405 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahama H, Masuko-hongo K, Tanaka A, Kawa Y, Ohta N, Yamamoto K, Mizoguchi M, Nishioka K, Kato T.: "T-cell clonotypes specific for dermatophagoides pteron_yssinus in the skin lesions of patients with atopic dermatitis"Human Immunol. 63. 558-566 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kono H, Suzuki T, Yamamoto K, Okada M, Yamamoto T, Honda Z: "Spatial raft coalescence represents an initial step in FcγβR signaling"J Immunol. 169. 196-203 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawahata K, Misaki Y, Yamaguchi M, Tsunekawa S, Setoguchi K, Miyazaki J, Yamamoto K: "Peripheral tolerance to a nuclear autoantigen : dendritic cells expressing a nuclear autoantigen lead to persistent anergic state of CD4+ autoreactive T cells after proliferatio"J Imnunol. 168. 1103-1112 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada R.et al.: "Peptidylarginine deiminase type4 : identification of a rheumatoid arthritis-susceptible gene."Trends Mol Med.. 9. 503-508 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki K.et al.: "High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis."Scand J Rheumatol.. 32. 197-204 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tokuhiro S.et al.: "An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis."Nature Genet.. 35. 341-348 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tahara H.et al.: "Reconstitution of CD8^+ T cells by retroviral transfer of the TCR αβ-chain genes isolated from a clonally expanded P815-infiltrating lymphocyte."J Immunol.. 171. 2154-2160 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki A.et al.: "Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis."Nature Genet.. 34. 395-402 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sekiya T.et al.: "Variations in the human Th2-specific chemokine TARC gene."Immunogenetics. 54. 742-745 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawahata K. et al.: "Peripheral tolerance to a nuclear autoantigen ; dendritic cells expressing a nuclear autoantigen lead to persistent anergic state of CD4^+ autore active T cells after proliferation"J. Immunol.. 168. 1103-1112 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawahata K. et al.: "Generation of CD4^+ CD25^+ regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from nonauto reactive T cells by endogenous TCR expressin"J. Immunol.. 168. 4399-4405 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iikura M. et al.: "Streptmycininduced anaphylactic shock during oocyte retrieval procedures for in vitro fertilization"J. Allergy. Clin. Immunol.. 109. 571-572 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kono H.et al.: "Spatial raft coalescence represents and initial step in FcγBR signaling"J. Immunol.. 169. 193-203 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshimura C. et al.: "Activation makers of human basophils : CD69 expression is strongly and preferentially induced by IL-3"J. Allergy. Clin. Immunol.. 109. 817-823 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahama H. et al.: "T-cell clonotypes specific for dermatophagoides pteronyssinus in the skin lesions of patients with atopic dermatitis"Human. Immunol.. 63. 558-566 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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