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THE ANALYSIS OF THE MECHANISM OF ALLOGRAFT REJECTION USING KNOCK OUT MICES

Research Project

Project/Area Number 09671384
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TOMITA Yukihiro  DEPARTMENT OF CARDIOVASCULAR SURGERY FACULTY OF MEDICINE KYUSHU UNIVERSITY ASSISTANT PROFESSOR, 医学部, 助手 (90180174)

Co-Investigator(Kenkyū-buntansha) KURISU Kazuhiro  DEPARTMENT OF CARDIOVASCULAR SURGERY FACULTY OF MEDICINE KYUSHU UNIVERSITY ASSIS, 医学部, 助手 (70294923)
NISIMURA Yousuke  DEPARTMENT OF CARDIOVASCULAR SURGERY FACULTY OF MEDICINE KYUSHU UNIVERSITY ASSIS, 医学部, 助手 (50301338)
岸原 健二  九州大学, 生体防御医学研究所, 助手 (80214774)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsCD4+ T cells / CD4 and CD8 knockout mice / xenografts / discordant / skin graft / 抗原認識 / CD4 / CD8
Research Abstract

An essential role of murine CD4+ T cells in immune reactivity and skin graft rejection in discordant xenogeneic combinations have been reported. The present study was conducted in order to further clarify the roles of CD4+ and CD8+ T cells in discordant skin xenograft rejection, by using CD4 and CD8 knockout [C57BL/6 Cr Sic (B6 ; H-2b) background] mice. When human skins were grafted on CD8 knockout mice or B6 mice, both hosts rejected human skin grafts within 12 days after grafting. By contrast, survival of human skin grafts was significantly prolonged in CD4 knockout mice [mean survival times (MST)= 19.3 _} standard deviation(SD)1.6days ; Medianl9days]. Fully allogeneic C3H/He Sic (H-2k) skin grafts were rejected within 14 days in CM knockout mice, suggesting that non-CD4+ T cells in CD4 knockout mice were immunocompetent for allograft rejection. In spleens of these recipient mice, CD8+ T cells seemed to be activated 10 days after human skin grafting. Immunohistological analysis revealed the infiltration of CD8+ T cells at the site of transplanted human skin on CD4 knockout mice. In order to further examine the role of CD8+ T cells in CD4 knockout mice, human skin grafting was performed on day 0 followed by administration of anti-CD8 monoclonal antibody (mAb) on days 0, 5, and 14. The administration of anti-CD8 mAb caused the significant prolongation of human skin graft survival. These results indicate the following two conclusions : 1) CD4+ T cells have an essential role in rejecting discordant human skin xenografts rapidly, 2) however, CD8+ T cells also are capable of rejecting discordant human skin xenografts.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] 富田幸裕: "マウス及び大動物における免疫寛容実験系より得られる知見" 「分子腎臓学(腎と透析 1998 Vol45増刊号)」. 45. 594-602 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 富田幸裕: "シクロホスファミド誘導性免疫寛容" 現代医療. 30・9. 2291-2299 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tomita Y,: "Lack of effect of cryopreservation on the class I and class II antigenicities of skin allografts" Transplant Proc. 30. 60-62 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 内田孝之: "T細胞によるDiscordant異種抗原の認識" 臨床免疫. 29・12. 1582-1586 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tomita Y: "Improved technique of heterotopic cervical heart transplantation in mice" Transplantation. 64・11. 1598-1601 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zhang OW,: "Fractionated dosing of cyclophosphamide for establishing long-lasting skin allografts 〓〓rviv stable mixed chimerism and intrathymic clonal deletion in mice primed with allogeneic spleen cel" Transplantation. 63・11. 1667-1673 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zhang QW,Mayumi H,Umesue M,Tomita Y,Nomoto K,Yasui H: "Fractionated dosing of cyclophosphamide for establishing long-lasting skin allograft survival, stable mixed chimerism and intrathymic clonal deletion in mice primed with allogeneic spleen cells" Transplantation. 63 (11). 1667-1673 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tomita Y,Zhang QW,Yoshikawa M,Uchida T,Nomoto K,Yasui H: "Improved technique of heterotopic cervical heart transplantation in mice" Transplantation. 64 (11). 1598-1601 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tomita Y,Zhang QW,Yoshikawa M,Uchida T,Nomoto K,Yasui H: "Lack of effect of cryopreservation on the class I and class II antigenicities of skin allografts" Transplant Proc. 30. 60-62 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 富田幸裕、: "拒絶反応と免疫寛容誘導:マウス及び大動物における免疫寛容実験系により得られる知見" 「分子腎臓病学(腎と透析 1998 Vol45増刊号)」. 45. 594-602 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 富田幸裕、: "シクロホスファミド誘導性免疫寛容" 現代医療. 30・9. 2291-2299 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomita Y,: "Lack of effect of cryopreservaion on the class I and class II antigenicities of skin allografts" Transplant Proc. 30. 60-62 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 内田孝之、: "T細胞によるDiscordant異種抗原の認識" 臨床免疫. 29・12. 1582-1586 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomita Y: "Improved technique of heterotopic cervical heart transplantation in mice" Transplantation. 64・11. 1598-1601 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Zhang QW: "Fractionated dosing of cyclophosphamide for establishing long-lasting skin allograft survive stable mixed chimerism and intrathymic clonal deletion in mice primed with allogeneic spleen cell" Transplantation. 63・11. 1667-1673 (1997)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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