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Molecular immunological investigation of animal model of Vogt-Koyanagi-Harada disease

Research Project

Project/Area Number 13671817
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionAKITA UNIVERSITY

Principal Investigator

SAKURAGI Shozo  Akita University School of Medicine, Proffesor, 医学部, 教授 (80006767)

Co-Investigator(Kenkyū-buntansha) KONNO Seiki  Akita University School of Medicine Research Associate, 医学部, 助手 (00312710)
YAMAKI Kunihiko  University School of Medicuie, Associate Proffesor, 医学部, 助教授 (20125751)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsVKH disease / Tyrosinase family proteins / T cell / T cell clone / animal model / Dendritic Cell / Tyrosinase related protein 1 / Animal model / Tyrosinase TRP1 / T cell clonl / 前房水 / auto reactive T cell
Research Abstract

We had established animal model of Vogt-Koyanai-Harada (VKH) disease. This model was induced by immunization of tyrosinase family proteins and the histologic findings of this disease was almost identical to that of human VKH disease.
We had done lymphocyte proliferation assay against tyrosinase family proteins using PBMC of acute and untreated stage of VKH disease patients. These lymphocytes showed proliferative response against one or more of the peptides derived from tyrosinase and/or TRP1. From these facts, we proposed that the target antigens of VKH disease are tyrosinase family proteins.
Then, we established T cell clone from PBMC of the VKH disease patients. The TCCs from VKH disease patients showed reactivity against the peptides that can interact with the HLA BRB1*04Q5. These TCCs were Thl cells and may play important role to the induction of the disease.
Finally, we established TCCs from aqueous humors and cerebrospinal fluid (CSF) of VKH disease patients. We could establish TCCs from 7 of the fresh, and untreated stage of VKH disease patients. Many TCCs were established and 30 clones, 21 from aqueous humor and 9 from CSF were tested the reactivity against tyrosinase family proteins. Surprisingly, 10/21 of TCCs from aqueous humor and 2/9 of TCCs from CSF showed proliferative response against tyrosinase or TRP1. These ratios were very high. We are now analyzing the T cell receptor (TCR) with RT-PCR SSCP. These methods may reveal the T cells that cause the autoimmune disease.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Yamaki K: "Ocular and extraocular inflammation induced by immunization of tyrosinase related protein 1 and 2 in Lewis rat"Exp Eye Res. 71. 361-369 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaki K: "Tyrosinase family proteins are antigens specific to Vogt-Koyanagi-Harada disease"J. Immunol.. 165. 7323-7329 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaki K: "Identification of Autoreactive T Cells in Vogt-Koyanagi-Harada Disease"Invest Ophthalmol Vis. Sci. 42. 2004-2009 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaki K: "Establishment and characterization of the T cell clones from the aqueous humons and cerebrospinal fluids with vogt-koyanagi-Harada disease patients"Akita. J. Med. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaki K., Konndo I., Nakamura H., Miyano M., Konno S., Sakuragi S.: "Ocular and extraocular inflammation induced by immunization of tyrosinase related protein 1 and 2 in Lewis rats."Exp Eye Res.. 71. 361-369 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaki K., Gocho K., Hayakawa K., Konndo I., Sakuragi S.: "Tyrosinase family proteins are antigens specific to Vogt-Koyanagi-Harada disease."J. Immunol.. 165. 7323-7329 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Gocho K., Kondo I., Yamaki K.: "Identification of autoreactive T cells in Vogt-Koyanagi-Harada disease."Invest. Opthalmol. Vis. Sci.. 42. 2004-2009 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaguchi M., Gocho K., Yamaki K.: "Establishment and characterization of the T cell clones from the aqueous humors and cerebrospinal fluids with Vogt-Koyanagi-Harada disease patients."Akita. J. Med.. 30 in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary

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Published: 2001-04-01   Modified: 2016-04-21  

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