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Tolerance Induction for Rat Liver Transplantation

Research Project

Project/Area Number 11671248
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

NISHIZAKI Takashi  Kyushu University Hospital, Instructor, 医学部・附属病院, 助手 (70253416)

Co-Investigator(Kenkyū-buntansha) 野本 健一  九州大学, 医学部, 助手 (50315090)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsliver transplantation / tolerance / bone marrow cell / chimerism / 遺伝子導入 / ミクロキメリズム
Research Abstract

Background. We previously established a cyclophosphamide (CP)-induced tolerance system in rodent skin graft models. In this study, we applied this system to rat liver transplantation.
Methods. Lewis recipients were inoculated on day -2 with spleen and bone marrow cells (SC+BMC) from Dark Agouti (DA) donors, followed by 100 mg/kg CP on day 0. On day 25, DA livers were orthotopically grafted. We assessed the alloresponses to the donors of the long-term surviving recipients, using the second skin grafting and in vitro assay.
Results. The recipients that had been treated with SC+BMC and CP survived for more than 165 days. None of control group that received SC+BMC alone (mean survival times [MST]=13.8 days), CP alone (MST=40.0), SC+BMC from third-party PVG rats and CP (MST=45.0), or no treatment (MST=13.8) survived over 50 days. The donor-specific tolerance was confirmed by second skin grafts onto recipients with permanent DA liver grafts, which accepted DA skins (MST>75) but not PVG (MST=8.3). However, the lymphocytes from the tolerant recipients showed alloresponse to DA in vitro. To investigate whether the T helper type 2 deviation contributed to this "split tolerance, " we assessed the production of cytokines in mixed lymphocyte reaction. Interleukin 2 and interferon-[gamma] were detected but interleukin 4 was not.
Conclusions. These data showed that this protocol induced split tolerance in rat liver transplantation and, furthermore, the mechanism of split tolerance was not due to T helper 2 deviation.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] 岡野慎二 他: "CYCLOPHOSPHAMIDE-INDUCED TOLERANCE IN RAT ORTHOTOPIC LIVER TRANSPLANTATION"Transplantation. 71. 447-456 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shinji Okano et al: "CYCLOPHOSPHAMIDE-INDUCED TOLERANCE IN RAT ORTHOTOPIC LIVER TRANSPLANTATION"Transplantation. 71. 447-456 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 岡野慎二 他: "CYCLOPHOSPHAMIDE-INDUCED TOLERANCE IN RAT ORTHOTOPIC LIVER TRANSPLANTATION"Transplantation. 71. 447-456 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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