Analysis of Rejection Mechanism and Indutcion of Unresponsiveness in Organ Transplantation
| Project/Area Number |
63570736
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Hokkaido University |
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Principal Investigator |
TOGASHI Masaki Hokkaido University School of Medicine, Associate Prof., 医学部, 助教授 (50041843)
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| Co-Investigator(Kenkyū-buntansha) |
SEKI Toshimori Hokkaido University Medical Hospital, Instructor, 医学部附属病院, 助手 (70196947)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1989: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | Major histocompatibility complex (MHC) / Inbred rat / Renal transplantation / Rejection / Anti-Ia monoclonal antibody / Spleen cell / Mixed lymphocyte reaction (MLR) / Unresponsiveness / ラット主要組織適合抗原 / ラット腎移植 / ラット皮膚移値 / deoxyspergualin / FACScan |
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| Research Abstract |
It is well known that the major histocompatibility complex (MHC) plays an important role as to whether a graft is accepted or rejected. In the present study, rat renal allografting was performed to investigate the most effective methods that induce immunological unresponsiveness.
1. Rejection model
TO (RT1^u), LEW (RT1^l), F344 (RT1^<lv>) rats were used as donors, and WKAH (RT1^k) rats as recipients. All these grafts were rejected within 16 days.
2. Experiments for prolongation of allograft survival
(1) Anti-Ia monoclonal antibody : The donor (F344) kidney was perfused with 1mg of anti-F344-Ia antibody (4B4) before transplantation, then the perfused graft was transplanted to WKAH rats (perfusion group). To make another experiment, we administered anti-recipient-Ia antibody (1E4) intravenously to WKAH rat after the perfused kidney was transplanted (perfusion^+iv group). Mean survival time of these 2 group prolonged significantly. However, there was no significant long suvivor.
(2) Preimmunza
… More
tion with donor strain spleen cells : The recipient rat (WKAH) was preimmunized with 5x10^7 donor strain (TO) spleen cells 1 week prior to transplantation. Six of 8 preimmunized rat survived more than 192 days.
(3) Short term administration of 15-deoxyspergualin (DSG) : TO rat kidney was transplanted to WKAH rat. In DSG group, 5mg/kg/day DSG was administered intramuscularily for 4 days from the 4th postoperative day. The short term administration (only 4 days) of DSG induced indefinite allograft survival.
3. Analysis of mechanisms of long term surviving
After renal allografting was performed from TO to preimmunized WKAH rats, recipients sera suppressed MLR nonspecifically for 2 weeks after grafting, but had no suppressive effect after 4 weeks. OX 8 positive cells continuously suppressed MLR specifically in donor type cells. In the DSG group, WKAH rat accepted TO skin graft, but rejected the skin grafts from other strain. These data indicated that the unresponsiveness induced by DSG was donor specific. Less
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Report
(4 results)
Research Products
(12 results)
