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New approach for indusing dunor specific tolerance using over deluevy of alloantigen

Research Project

Project/Area Number 13671254
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionTeikyo University

Principal Investigator

NIIMI Masanori  Teikyo University,medicine,Associate Prof., 医学部, 助教授 (80198415)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsToleronce / Oral delivery / alloantigen / 抗原ペプチド / 移植
Research Abstract

Oral administration can induce unresponsiveness to protein antigens. However, a number of trials using oral administration of alloantigens have failed to induce operational tolerance. I demonstrated that multiple oral deliveries of donor alloantigen induced modest prolongation of a single MHC mismatched cardiac allograft. When anti-CD4 monoclonal antibody (mAb) was administered before the first oral delivery, all grafts survived for over 100 days. Moreover, a single oral delivery of alloantigen plus anti- CD4 mAb induced indefinite survival of not only a single MHC mismatched but also fully allogeneic cardiac grafts. Orally delivered cells could not be detected in mice, suggesting that the indirect antigen recognition was involved. In fact, oral delivery of K^b molecule plus anit-CD4 mAb induced indefinite survival. Furthermore, oral delivery of K^b combined with anti-CD4 mAb induced survival of fully allogeneic cardiac grafts, suggesting that the linked suppression may be involved in the induction phase. Fina ly, Oral delivery of ovalbumine plus anti-CD4 mAb induced prolonged survival of grafts when the ovalbumine was injected orally again at the time of transplantation. These findings provide a lot of helpful evidences for clinical application of oral tolerance to alloantigen.

Report

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

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Aramaki O: "High dose of antithrombin III induces indefinite survival of fully allogeneic cardiac grafts and generates regulatory cells"Transplantation. 75(2). 217-220 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akiyama Y: "Intratracheal delivery of a single major histocompatibility complex class I peptide induced prolonged survival of fully allogeneic cardiac grafts and generated regulatory cells"Human Immunology. 63(10). 888-892 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akiyama Y: "B7/CTLA4 pathway is essential for generating regulatory cells after intratracheal delivery of alloantigen in mice"Transplantation. 74(5). 732-738 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Niimi M: "Operational tolerance induced by pretreatment with donor dendritic cells under blockade of CD40 pathway"Transplantation. 72(9). 1556-1562 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akiyama Y, Shirasugi N, Aramaki O, Matsumoto K, Shimazu M, Kitajima M, Ikeda Y, Niimi M.: "Intratracheal delivery of a single major histocompatibility complex class I peptide induced prolonged survival of fully allogeneic cardiac grafts and generated regulatory cells"Hum Immunol. 63(10). 888-92 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akiyama Y, Shirasugi N, Uchida N, Matsumoto K, Kitajima M, Bashuda H, Yagita H, Okumura K,Aramaki O, Niimi M.: "B7/CTLA4 pathway is essential for generating regulatory cells after intratracheal delivery of alloantigen in mice"Transplantation. 74(5). 732-8 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aramaki O, Takayama T, Yokoyama T, Takano S, Akiyama Y, Shibutani S, Matsumoto K, Shimazu M, Kitajima M, Ikeda Y, Shirasugi N, Niimi M.: "High dose of antithrombin III induces indefinite survival of fully allogeneic cardiac grafts and generates regulatory cells"Transplantation. 75(2). 217-20 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Niimi M, Shirasugi N, Ikeda Y, Kan S, Takami H, Hamano K.: "Operational tolerance induced by pretreatment with donor dendritic cells under blockade of CD40 pathway"Transplantation. 72(9). 1556-62 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Niimi M.: "The technique for heterotopic cardiac transplantation in mice: experience of 3000 operations by one surgeon"J Heart Lung Transplant. 20(10). 1123-8 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aramaki O: "High dose of anfithrombin III"Transplantation. 75(2). 217-220 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akiyama Y: "Intratracheal delivery"Human Immunology. 63(10). 888-892 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akiyama Y: "B7/CTLA4 pathway"Transplantation. 74(5). 732-738 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Niimi: "Operational tolerance"Transplantation. 72(9). 1556-1562 (2001)

    • Related Report
      2002 Annual Research Report

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

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