THE ANALYSIS OF THE MECHANISM OF ALLOGRAFT REJECTION USING KNOCK OUT MICES
| Project/Area Number |
09671384
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
TOMITA Yukihiro DEPARTMENT OF CARDIOVASCULAR SURGERY FACULTY OF MEDICINE KYUSHU UNIVERSITY ASSISTANT PROFESSOR, 医学部, 助手 (90180174)
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| 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)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| 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)
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| Keywords | CD4+ T cells / CD4 and CD8 knockout mice / xenografts / discordant / skin graft / 抗原認識 / CD4 / CD8 |
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| 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.
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Report
(3 results)
Research Products
(15 results)
