• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Induction of immuno-tolerance for allografts using bone marrow stem cells transffered with donor major histocompatibility complex gene.

Research Project

Project/Area Number 07457294
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionOsaka University

Principal Investigator

NAKATA Seizo  Osaka-University, 1st dept.surg., assistant prof., 医学部, 助教授 (50116068)

Co-Investigator(Kenkyū-buntansha) FUKUSHIMA Noritaka  Osaka-University, 1st dept.surg., assistrant, 医学部, 助手 (30263247)
ITO Toshinori  Osaka-University, 1st dept.surg., lecturer, 医学部, 講師 (20231152)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1996: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1995: ¥4,400,000 (Direct Cost: ¥4,400,000)
Keywordsimmuno-tolerance / MHC / Bone marrow stem cell / Intrathymic injection / Gene transffer / 主要組織適合性抗原(MHC)遺伝子
Research Abstract

We attempt to induce donor-specific immuno-tolerance for allografts by the method of intrathymic injection with donor's MHC expressing cells.
Fully allogeneic fresh bone marrow cells (BMC) of BUF (RT1^b) rats were intrathymically injected into WF (RT1^u) rats at the same time of BUF cardiac allografts with a short course treatment of ALS and FK506, resulting in prolonged graft survival (MST >210 days). Those rats treated with syngeneic IT and allogeneic IV rejected BUF grafts within 28.8 and 54.4 days, respectively. Long-term tolerant rats had a significantly decreased fT cp (frequency of Tc precursors), and fThp (frequency of IL-2 producing Th precursors), compared to naive rats. In cardiac allografts in tolerant rats, RT-PCR method for cytokines showed that glFN gene expression was completely inhibited at the chronic phase. On day 130 postgrafting, tolerant WF rats accepted donor BUF skin grafts for more than 120 days, but not third-party LEW skin grafts. Then we concluded that perfect induction of donor-specific tolerance was obtained by IT of donor BMC performed at the same time as cardiac transplantation.
Next, we tried to transfer PVG-R1 donor's MHC gene (RT1A^a) into recipient BUF cells. Expression vector of RT1A^a gene containing CMV-enhancer and actin promotor was transffered into BUF hepatoma cell line (7316A) by electroporlation, then we obtained many stable-transfected cell lines. However enough RT1A^a protein expression was not detected neither by immuno-blotting nor by FACS analysis using anti-RT1A^a monoclonal antibody. Also in vivo intrathymic injection of radiated transfectants cells could not induce immuno-tolerance for allografts. We considered that more generous expression of MHC molecules on trnsffered cells were indispensable to acquire donor-specific immuno-tolerance, such as developping more efficient expression vector for MHC gene.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] A. ITO et al.: "Donor-specific tolerance by perioperative intrathymic injection of bone marrow cells in rat cardiac allograft model" Transplantation. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A. ITO et al.: "A unique mechanism of tolerance by perioperative intrathymic injection of bone marrow cells with a short course of ALS and FK506 in rat cardiac allograft model" Transplant Proceedings. 29. 1137-1138 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A. ITO et al.: "Induction of tolerance in rat cardiac allograft model by intrathymic injection of donor bone marrow cells" Transplant Proceedings. 27. 1607-1608 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 伊藤章ら: "胸腺内ドナー骨髄細胞投与による特異的免疫寛容の誘導" 今日の移植. 8. 335- (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Ito et al.: "Donor-specific tolerance by perioperative intrathymic injection of bone marrow cells in rat cardiac allograft model" Transplantation. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Ito, T.Ito, W.Kamiike, A.Moriguchi, A.Ohkawa, F.Uchikoshi, S.Tanaka, S.Nakata, and H.Matsuda: "A unique mechaism of tolerance by perioperative intrathymic injection of bone marrow cells with a short course of ALS and FK506 in rat cardiac allograft model" Transplant Proceedings. 29. 1137-1138 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Ito, T.Ito, W.Kamiike, S.Nozaki, F.Uchikoshi, S.Tanaka, A.Kuhara, A.Moriguchi, M.Miyata, S.Nakata, R.Shirakura, and H.Matsuda: "Induction of tolerance in rat cardiac allograft model by intrathymic injection of donor bone marrow cells" Transplant Proceedings. 27. 1607-1608 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Ito, T.Ito, W.Kamiike, A.Moriguchi, S.Nakata, R.Shirakura and H.Matsuda: "Induction of tolerance in rat cardiac allograft model by intrathymic injection of donor bone marrow cells" Konnichi-no-Ishoku (in Japanese). 8. 335-339 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.ITO et al.: "Induction of tolerance in rat cardiac allograft model by intrathymic injection of donor bone marrow cells" Transplantation Proceedings. 27. 1607-1608 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 伊藤章ら: "胸腺内ドナー骨髄細胞投与による特異的免疫寛容の誘導" 今日の移植. 8. 335- (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.ITO et al.: "Donor-specific tolerance by perioperative intrathymic injection of bone marrow cells in rat cardiac allograft model" Transplantation. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] A.ITO et al.: "A unique mechanism of tolerance by perioperative intrathymic injection of bone marrow cels with a short course of ALS and FK506 in rat cardiac allograft model" Transplantation Proceedinga. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 伊藤章・伊藤壽記・上池渉・森口聡・中田精三・白倉良太・松田暉: "胸腺内ドナー骨髄細胞投与による特異的免疫寛容の誘導" 今日の移植. 8. 335- (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] A.Ito,T.Ito,W.Kamiike,S.Nozaki,F.Uchikoshi,T.Tanaka,A.Kuhara,A.Moriguchi,M.Miyata,S.Nakata,R.Shirakura: "Induction of Tolerance in Rat Cardiac Allograft Model by Intrathymic Injection of Donor Bore Mawow Cells" Transplantation Proceedings. 27. 1607-1608 (1995)

    • Related Report
      1995 Annual Research Report

URL: 

Published: 1995-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi