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Studies on molecular mechanisms of autoimmune diseases

Research Project

Project/Area Number 05044166
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionOsaka University

Principal Investigator

KISHIMOTO Tadamitsu  Osaka University Medical School, 医学部, 教授 (10093402)

Co-Investigator(Kenkyū-buntansha) DAVIS M.  Stanford University School of Medicine, 助教授
REINHARZ E.  Dana-Farber Cancer Institute, 助教授
KIYONO H.  Department of Oral Biology, University of Alabama, 教授
LOH D.  Washington University School of Medicine, 助教授
NISHIKAWA Shiniti  Kyoto University Faculty of Medicine, 医学部, 教授 (60127115)
HIRANO Tosio  Osaka University Medical School, 医学部, 教授 (40136718)
TAKATSU Kiyoshi  The Institute of Medical Science, The University of Tokyo, 医科学研究所, 教授 (10107055)
OKUMURA Kou  Juntendou University School of Medicine, 医学部, 教授 (50009700)
HONJO Tasuku  Kyoto University Faculty of Medicine, 医学部, 教授 (80090504)
SASAZUKI Takehiko  Medical Institute of Bioregulation, Kyushu University, 生体防御医学研究所, 教授 (50014121)
Project Period (FY) 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordsself-tolerance / autoimmune disease / apoptosis / CD5^+B cells / adhesion molecule / B70 / MHC molecule / antigenic peptide
Research Abstract

Molecular mechanisms of self-tolerance and pathogenesis of autoimmune diseases are one of the central issues in the immunology. In order to peruse the following questions, the collaborative studies between immunologists in the US and Japan have been undertaken.
1.Molecular mechanism of positive and negative selection of T cells.
2.Antigenic peptides involved in autotolerance and autoimmune diseases.
3.Cytokines and their receptors and their relationship with autoimmune diseases.
4.Transgenic as well as knock out mice in the studies on the immune regulation.
5.Interaction between MHC and autigenic peptides and their recognition by T cells.
6.Regulation of the expression of the HLA multi-gene family and autoimmune diseases.
The outcome obtained by these collaborative studies are as follows ;
Dr.T.Honjo spent most of his time by discussing with his latest results about B lymphocyte tolerance and treatment of autoimmune diseases with prominent immunologists in NIH like Dr.W.Paul, M.Leonald, J.Ashw … More ell, R.Schwartz and P.Mezinger. Honjo found that repeated injection of H_2O into the peritoneal cavity of New Zealand black mice reduced the frequency of autoimmune diseases. The result suggests that CD5^+B cells might be involved in the onset of autoimmune diseases in autoimmune prone New Zealand black mice. During such discussion, he reached agreement to organize International Conference on Programed Cell Death at NIH in August of 1994.
By the collaboration with the scientists of Department of Genetics. Stanford Medical Center, and DNAX and by exchanging experimental materials each other, Dr.K.Okumura succeeded to clone the unknown gene coding one of the most important adhesion molecules (B70), in terms of T cell activation on macrophage and B cell.
Dr.T.Sasazuki visited professors Jack Strominger, Don Willey, and Chikao Morimoto at Harvard University (Boston), Bo Dupont at Sloan Ketterling Cancer Institute (New York) and Hugh O.McDevitt, Mark Davis and Garry Fathman at Stanford University (Staford) to discuss and exchange the new informations as well as reagents to persue collaboratory work on "Regulation by the products of HLA multigene family" as followings :
1.Interaction of HLA-DR molecules and antigenic peptides based on the crystallography of HLA-DR1 (J.Strominger, D.Willey)
2.Immune regulation through the interaction of adhesion molecules (C.Morimoto).
3.Signal transduction through HLA class II molecules (B.Dupont)
4.Role of MHC class II molecules in regulating the T cell repertoire using HLA class II and T cell receptor transgenic mice (H.O.McDevitt, M.Davis, G.Fathman). Less

Report

(1 results)
  • 1993 Final Research Report Summary
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Azuma M.,Ito D.,Yagita H.,Okumura K.,and Philips J.H.,Lanier,L.L.and Somoza C.: "B70 antigen is a second ligand for CTLA-4 and CD28." Nature. 366. 76-79 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsubata T.,Wu J.and Honjo T.: "B cell apoptosis induced by antigen receptor crosslinking is blocked by T cell signal through CD40." Nature. 364. 645-648 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nishitani S.,Tsubata T.,Murakami M.,Okamoto M.and Honjo T.: "The bcl-2 gene product inhibits clonal delition of self-reactive B lymphocytes in the periphery but not in the bone marrow. and processed DRα-derived pepitde." J.Exp.Med.178. 1247-1254 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Fukui Y.,Yamamoto K.,Sasazuki T.,Yokoyama N.,Iwanaga T.,Kurashima C.,Esaki Y.,Kimura A.,Akashi T.,Hirokawa K.and: "Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in aquisition of T cell tolerance to self-superantigens" Eur.J.Immunoi.23. 1678-1686 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Murakami M.,Hibi M.,Nakagawa N.,Nakagawa T.,Yasukawa K.,Yamanishi K.,Taga T.and Kishimoto T.: "IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase." Science. 260. 1808-1810 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Akira S.,Nishio Y.,Inoue M.,Wang X.,Wei S.,Matsusaka T.,Yoshida K.,Sudo T.,Naruto M.and Kishimoto T.: "Molecular cloning of APRF,a novel ISGF3 p91-related transcreption factor involved in the gp130-mediated signaling pathway." Cell. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Azuma M., Ito D., Yagita H., Okumura K., and Philips J.H., Lanier, L.L. and Somoza C.: "B70 antigen is a second ligand for CTLA-4 and CD28." Nature. 366. 76-79 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsubata T., Wu J. and Honjo T.: "B cell apoptosis induced by antigen receptor crosslinking is blocked by T cell signal through CD40." Nature. 364. 645-648 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nishitani S., Tsubata T., Murakami M., Okamoto M. and Honjo T.: "The bcl-2 gene product inhibits clonal delition of self-reactive B lymphocytes in the periphery but not in the bone marrow." J.Exp.Med.178. 1247-1254 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Fukui Y., Yamamoto K., Yokoyama N., Iwanaga T., Kurashima C., Esaki Y., Kimura A., Akashi T., Hirokawa K. and Sasazuki T: "Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in aquisition of T cell tolerance to self-superantigens and processed DRalpha-derived pepitde." Eur.J.Immunoi.23. 1678-1686 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Murakami M., Hibi M., Nakagawa N., Nakagawa T., Yasukawa K., Yamanishi K., Taga T. and Kishimoto T.: "IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase." Science. 260. 1808-1810 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Akira S., Nishio Y., Inoue M., Wang X., Wei S., Matsusaka T., Yoshida K., Sudo T., Naruto M. and Kishimoto T.: "Molecular cloning of APRF, a novel ISGF3 p91-related transcription factor involved in the gp130-mediated signaling pathway." Cell. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary

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Published: 1993-04-01   Modified: 2016-04-21  

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