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

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671254
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Teikyo University
• Principal Investigator: NIIMI Masanori Teikyo University,medicine,Associate Prof., 医学部, 助教授 (80198415)
• Project Period (FY): 2001 – 2002
• Keywords: Toleronce / Oral delivery / alloantigen / 抗原ペプチド

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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