| Project/Area Number |
08457294
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HARIHARA Yasushi University of Tokyo Hospital Intemal Medicine Lecturer, 医学部・附属病院, 講師 (10189714)
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| Co-Investigator(Kenkyū-buntansha) |
KITA Yoshiaki University of Tokyo Hospital Intemal Medicine Assistant Professor, 医学部・附属病院, 助手 (00292904)
HIRATA Masaru University of Tokyo Hospital Intemal Medicine Assistant Professor, 医学部・附属病院, 助手 (60282670)
KUBOTA Keiichi University of Tokyo Hospital Intemal Medicine Lecturer, 医学部・附属病院, 講師 (70260388)
三木 健司 東京大学, 医学部・附属病院, 助手 (10242059)
青柳 信嘉 東京大学, 医学部・附属病院, 助手 (90292903)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | xenotransplantation / hyperacute rejection / neonatal tolerance / intrathymic injection / NK cells / delayed xenograft rejection / 経門脈的投与 |
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| Research Abstract |
Xenotransplantation is one of the procedures to resolve donor organ shortage in allogeneic combination. Mechanisms of hyperacute rejection and/or delayed xenograft rejection and their treatment have to be clarified and established for the clinical application of xenotransplantation. In this study we investigated 1) the possibility of induction of neonatal tolerance in xenogeneic combination and 2) the role of NK cells in rejection in a concordant xenogeneic combination.
With regard to neonatal tolerance in xenogeneic combination, lymphocytes obtained from hamster spleen were injected into intraperitoneal cavity, vein, portal vein or thymus of Lewis rats within 24 hours after birth as a pretreatment. Induction of tolerance was examined by the hamster heart grafting performed 8 weeks after the pretreatment. So far, even by the intrathymic injection of donor species lymphcytes which was suspected as most powerful tolerogenic pretreatment, neonatal tolerance could not be induced between the xenogeneic combination.
With regard to the role of NK cells in rejection between the concordant xenogeneic combination, NK activity, subsets of lymphocytes, and NK cell distribution in the graft were examined in a hamster-to-rat heart or liver transplantation model. In conclusion, NK cells were activated early after transplantation and were continued to be activated until the rejection phase in the xenogeneic model when compared with the allogeneic model.
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