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The analysis of genes involved in the control of Th1/Th2 balance and its role in immune diseases

Research Project

Project/Area Number 10833004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 免疫の制御機構
Research InstitutionHOKKAIDO UNIVERSITY (1999)
Tokai University (1998)

Principal Investigator

NISHIMURA Takashi  Hokkaido University, Institute for immunological Science, Professor, 免疫科学研究所, 教授 (30143001)

Co-Investigator(Kenkyū-buntansha) 若菜 茂晴  実験動物中央研究所, 遺伝子解析, 研究員
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsTh1 / Th2 balance / immunoregulatory genes / cytokine / aller / immune diseases / immune predisposition / atopy / Th2 / 免疫制御 / 遺伝子 / 免疫疾患
Research Abstract

Immune system plays a critical role for maintaining the homeostasis of our body as well as nervous and endocrine systems. Generally, our body is protected from various diseases by a strict immunorecognition and immunoregulation mechanisms. However, once, the imbalance of immunoregulation is occurred, it becomes causes of various immune diseases. Recently, it has been clarified that immune balance is regulated by two helper T (Th) cell subsets, Th1 and Th2. Therefore, it is a great important issue to investigate the role of Th1/Th2 balance in various diseases to develop new diagnosis and treatment for immune diseases. Here, we investigated the control mechanisms of Th1/Th2 balance and its role in immune diseases. Moreover, we also pursued factors involved in genetically controlled Th1/Th2 balance to make clear the factors related to genetic immune diseases.
As results, we demonstrated new findings as described in the following ;
1. We esiablished new animal models for tumor, allergy and liver injury using antigen-specific Th1 and Th2 cells. It was demonstrated that Th1 and Th2 cells derived from the same naive Th cells exhibited totally distinct role during the onset of diseases in vivo.
2. The abnormality of Th1/Th2 balance in atopic dermatitis (AD) patients was demonstrated. CD4+T cells obtained from AD patients revealed reduced IFN-g producing ability. Moreover, quantitative and qualitative defect of CD4+CD45RO+ memory T cells reactive against PPD was clarified.
3. The genes involved in the control of Th1/Th2 balance was mapped on mouse chromosomes. One of the candidate genes was located nearby IL-4 receptor a gene, which is related to the incidence of atopic dermatis.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Nishimura T.: "The interface between innate and acquired immunity : Glycolipid antigen presentation by CD1d-expressing dendritic cells to natural killer T cells induces the differentiation of antigen-specific cytotoxic T lymphocytes"Int. Immunol.. (In press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato M.: "Functional heterogeneity among bone marrow-derived dendritic cells conditioned by Th1-and Th2-biasing cytokines for the generation of allogeneic cytotoxic T lymphocytes"Int. Immunol. (In press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitamura H.: "α-galactosylceramide induces early B-cell activation through IL-4 production by NKT cells"Cell. Immunol.. (In press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohmi Y.: "Tumor-specific targeting of T helper type 1 (Th1)cells by anti-CD3×anti-c-ErbB-2 bispecific antibody"Cancer Immunol. Immunother.. 48. 456-462 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuyama T.: "The quantitative and qualitative defect of CD4^+CD45RO^+ memory type T cells are involved in the adnormality of Th1-immunity in atopic dermatitis patients"Clin. Exp. Allergy. 29. 687-694 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishimura T.: "Distinct role of antihen-specific T helper type 1(Th1)and Th2 cells in tumor eradication in vivo"J. Exp. Med.. 190. 617-628 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 西村孝司: "接着分子のすべて"臨床免疫. 336 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 塚越茂: "これからの癌免疫療法〜21世紀に向かって〜"医薬ジャーナル社. 260 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishimura, T.: "The interface between innate and acquired immunity : Glycolipid antigen preseniation by CD1d-expressing dendritic cells to natural killer T cells induces the differentiation of antigen-specific cyiotoxic T lymphocytes"Int. Immunol. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato, M.: "Functional heterogeneity among bone marrow-derived dendritic cells conditioned by Th1- and Th2-biasing cyiokines for he generation of allogeneic cyiotoxic T lymphocytes"Int. Immunol. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitamura, H.: "α-galactosylceramide induces early B-cell activation tlnrough IL-4 production by NKT cells"Cell Immunol. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohmi, Y.: "Tumor-specific targeting of T helper type 1 (Th1) cells by anti-CD3 x anti-c-ErbB-2 bispecific antibody"Cancer Immunol. Immunother.. 48. 456-462 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuyama, T.: "The quantitative and qualitative defect of CD4ィイD1+ィエD1CD45R0ィイD1+ィエD1 memory type T cells are involved in the abnormality of Th1-immunity in atopic dermatitis patients"Clin. Exp. Allergy. 29. 687-694 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishimura, T.: "Distinct role of antihen-specific T helper type 1 (Th1) and Th2 cells In tumor eradlcatlon in vivo"J. Exp. Med.. 190. 617-628 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishimura, T.: "The interface between innate and acquired immunity : Glycolipid antigen presentation by CD1d-expressing dendritic cells to natural killer T cells induces the differentiation of antigen-specific cytotoxic T lymphocytes"Int. Immunol.. (In press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sato, M.: "Functional heterogeneity among bone marrow-derived dendritic cells conditioned by Th1- and Th2-biasing cytokines for the generation of allogeneic cytotoxic T lymphocytes"Int. Immunol.. (In press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitamura, H.: "α-galactosylceramide induces early B-cell activation through IL-4 production by NKT cells"Cell. Immunol.. (In press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohmi, Y.: "Tumor-specific targeting of T helper type 1(Th1) cells by anti-CD3 x anti-c-ErbB-2 bispecific antibody"Cancer Immunol. Immunother.. 48. 456-462 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuyama, T.: "The quantitative and qualitative defect of CD4^+CD45RO^+ memory type T cells are involved in the abnormality of Th1-immunity in atopic dermatitis patients"Clin. Exp. Allergy. 29. 687-694 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishimura, T.: "Distinct role of antihen-specific T helper type1 (Th1) and Th2 cells in tumor eradication in vivo"J. Exp. Mad.. 190. 617-628 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 西村 孝司: "接着分子のすべて"臨床免疫. 336 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 塚越 茂: "これからの癌免疫療法 〜21世紀に向かって〜"医薬ジャーナル社. 260 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitamura,H.: "The nalural killer T(NKT) cell ll gand α-galactosylceramlde demonstrates its im muno pot entiatl ating effect by inducing IL-12 production by dendritic cells and IL-12 receptor expression on NKT cell." J.Exp.Med. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yahata,T: "The es sentlal role of phorbol es ter-sensltive protein kinase C is ofor ms in activation-induced cell death of The1 cells" Eur.J.Immunol. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sato,M: "Functional skewing of bone marrow-derived dendritic cells by Th1-or The1-inducing cytoklnes" Immurol.letters. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsuyama,T: "The quantitative and qualitatlve defect of CD^<4+>CD 45RO^+ memory type T cell are involved in the abnormality of The1-immunlty in atopic dermatitis patients" Clin.Exp.Allergy. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kametani,Y: "Ex vivo evidence for asymmetric tyrosine phosphorylation of ZAP-70 on doubl-positive thymocytes in the positive selection process" Int.Immunol. 10. 1203-1210 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yahata,T: "Reconstituti on of immune systems in RAG2 mice by transfer with interliukin-12-jinduced spienic hematopoletic progenltor cells" Immunol.letters. 62. 165-170 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iwakabe,K: "The restraint stress drives a shift in Th1/Th2 balance toward Th2-dominant immunity in mice" Immunol.letters. 62. 39-43 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yahata,T: "Accumulation of IL-12-activated antitumor effectror cells intolymph nodes of tumor-bearing mice" Immunol.letters. 61. 127-133 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mori,T: "Involvement of Fas-mediated apoptosis in the hematopoetic progenitor cells of graft-versus-host reacti on-associated myelos uppression" Blood. 92. 101-107 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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