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Expression of MHC class II antigens on islet cells in the pathogenesis of Type I diabetes

Research Project

Project/Area Number 62480253
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionOsaka University

Principal Investigator

HANAFUSA Toshiaki  Osaka University Medical School Research Assistant, 医学部, 助手 (60164886)

Co-Investigator(Kenkyū-buntansha) MIYAGAWA Jun-ichiro  Osaka University Hospital Resident, 医学部附属病院, 医員 (00127721)
MIYAZAKI Atsushi  Osaka University Hospital Resident, 医学部附属病院, 医員
KONO Norio  Osaka University Medical School Assistant Professor, 医学部, 講師 (30093412)
TARUI Seiichiro  Osaka University Medical School Professor, 医学部, 教授 (00028341)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsType 1 (insulin-dependent) diabetes mellitus / Major histocompatibility complex (MHC) class II antigen / Pancreatic islet / insulitis / pathogenesis / autoimmunity / NODマウス
Research Abstract

This study has been performed to clarify the significance of major histocompatibiity complex (MHC) class II antigens on pancreatic beta-cells in the pathogenesis of Type 1 (insulin-dependent) diabetes mellitus.
In non-obese diabetic (NOD) mice, an animal model for Type 1 diabetes, I-A antigen, one of mouse MHC class II antigens, was observed in islet cells of all NOD mice examined. Double staining with anti-insulin, glucagon, somatostatin or pancreatic polypeptide antibodies revealed that I-A positive cells corresponded with insulin cells.
Following this observation, we examined the pancreas biopsy specimens from 7 newly diagnosed Type 1 diabetic patients. Several features were revealed including marked decrease of insuli-containing cells, preservation of glucagon-containing cells, and various degrees of expression of MHC class I and class II antigens in islet cells and endothelial cells within and around the islets. In one patient, MHC class II antigens were clearly detected in insulin-containing cells. Electron microscopical examination showed the presence of a few lymphocytes infiltrating some islets of another patient.
These results suggest that islet cells are destructed through immunological mechanisms and MHC class II antigens on insulin-containing cells may play an important role in the pathogenesis of Type 1 diabetes.

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] T.,Hanafusa;et al.: Diabetologia. 30. 104-108 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] K.,Yamada;et al: Best approach to the ideal therapy of diabetes mellitus. 155-157 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.,Hanafusa;et al: Diabetes. 37. 204-208 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.,Yamada;et al: Clin.Endocrinol.29. 29-34 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.,Hanafusa;et al: Diab.Nutr.Metab.in press. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.,Hanafusa;et al: Folia Endocrinol.Jap.64. 1228-1232 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S.,Tarui;T.,Hanafusa: "Frontiers in diabetes research:Lessons from animal diabetes" John Libbey & Company Ltd., 99-104 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S.,Tarui;T.,Hanafusa: "The diabetes annual 4" Elsevier Science Publishers, 609-620 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Hanafusa et al.: "Expression of class II major histocompatibility complex antigens on pancreatic B cells in the NOD mouse." Diabetologia. 30. 104-108 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Hanafusa et al.: "Induction of insulitis by adoptive transfer with L3T4+Lyt2-T-lymphocytes in T-lymphocyte-depleted NOD mice." Diabetes. 37. 204-208 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y. Yamada et al: "Exaggerated insulin secretory response in patients with insulinomas to midaglizole, a drug with alpha-2-adrenergic blocking activity." Clin. Endocrinol.29. 29-34 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Hanafusa et al: "Autoantibodies to islet cells and multiple organs in the NOD mouse." Diab. Nutr. Metab.in press. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Hanafusa et al: "Expression of major histocompatibility complex class II antigen on target cells in autoimmune endocrine diseases." Folia Endocrinol. Jap.64. 1228-1232 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S. Tarui; T. Hanafusa: Frontiers in diabetes research: Lessons from animal diabetes. John Libbey & Company Ltd., 99-104 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.Hanafusa;et al.: Diabetes. 37. 204-208 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] A.Miyazaki;et al.: Proc.of the Satellite Int.Symp.on Pathogenesis and Treatment of Type II Diabetes Mellitus. 44-48 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Y.Yamada;et al.: Clin.Endocrinol.29. 29-34 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] T.Hanafusa;et al.: Diab.Nutr.Metab.in press. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] T.Hanafusa;et al.: Folia Endocrinol.Jap.64. 1228-1232 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 山田研太郎 他: 糖尿病. 30. 453-455 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] S.Tarui;T.Hanafusa: "Frontiers in diabetes research:Lessons from animal diabetes II" John Libbey & Company Ltd., 99-104 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] S.Tarui;T.Hanafusa: "Diabetes annual 4" Elsevier Science Pub., 609-620 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Hanafusa T,: Diabetologia. 30. 104-108 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Hanafusa T,: Diabetologia. 37. 204-208 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Yamada Y,: Clin.Endocrinol.(1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Tarui S,: In:Lessons from Animal Diabetes II.

    • Related Report
      1987 Annual Research Report
  • [Publications] Tarui S,: In:The Diabetes Annual4. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Hanafusa T,: In:Immunotherapy of Type I Diabbetes and Selected Organ Specific Autoimmune Diseases.(1988)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2017-04-05  

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