Induction of immuno-tolerance for allografts using bone marrow stem cells transffered with donor major histocompatibility complex gene.
| Project/Area Number |
07457294
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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 |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
NAKATA Seizo Osaka-University, 1st dept.surg., assistant prof., 医学部, 助教授 (50116068)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Noritaka Osaka-University, 1st dept.surg., assistrant, 医学部, 助手 (30263247)
ITO Toshinori Osaka-University, 1st dept.surg., lecturer, 医学部, 講師 (20231152)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1996: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1995: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | immuno-tolerance / MHC / Bone marrow stem cell / Intrathymic injection / Gene transffer / 主要組織適合性抗原(MHC)遺伝子 |
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| Research Abstract |
We attempt to induce donor-specific immuno-tolerance for allografts by the method of intrathymic injection with donor's MHC expressing cells.
Fully allogeneic fresh bone marrow cells (BMC) of BUF (RT1^b) rats were intrathymically injected into WF (RT1^u) rats at the same time of BUF cardiac allografts with a short course treatment of ALS and FK506, resulting in prolonged graft survival (MST >210 days). Those rats treated with syngeneic IT and allogeneic IV rejected BUF grafts within 28.8 and 54.4 days, respectively. Long-term tolerant rats had a significantly decreased fT cp (frequency of Tc precursors), and fThp (frequency of IL-2 producing Th precursors), compared to naive rats. In cardiac allografts in tolerant rats, RT-PCR method for cytokines showed that glFN gene expression was completely inhibited at the chronic phase. On day 130 postgrafting, tolerant WF rats accepted donor BUF skin grafts for more than 120 days, but not third-party LEW skin grafts. Then we concluded that perfect induction of donor-specific tolerance was obtained by IT of donor BMC performed at the same time as cardiac transplantation.
Next, we tried to transfer PVG-R1 donor's MHC gene (RT1A^a) into recipient BUF cells. Expression vector of RT1A^a gene containing CMV-enhancer and actin promotor was transffered into BUF hepatoma cell line (7316A) by electroporlation, then we obtained many stable-transfected cell lines. However enough RT1A^a protein expression was not detected neither by immuno-blotting nor by FACS analysis using anti-RT1A^a monoclonal antibody. Also in vivo intrathymic injection of radiated transfectants cells could not induce immuno-tolerance for allografts. We considered that more generous expression of MHC molecules on trnsffered cells were indispensable to acquire donor-specific immuno-tolerance, such as developping more efficient expression vector for MHC gene.
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Report
(3 results)
Research Products
(14 results)
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[Publications] A.Ito, T.Ito, W.Kamiike, S.Nozaki, F.Uchikoshi, S.Tanaka, A.Kuhara, A.Moriguchi, M.Miyata, S.Nakata, R.Shirakura, and H.Matsuda: "Induction of tolerance in rat cardiac allograft model by intrathymic injection of donor bone marrow cells" Transplant Proceedings. 27. 1607-1608 (1995)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Publications] A.Ito,T.Ito,W.Kamiike,S.Nozaki,F.Uchikoshi,T.Tanaka,A.Kuhara,A.Moriguchi,M.Miyata,S.Nakata,R.Shirakura: "Induction of Tolerance in Rat Cardiac Allograft Model by Intrathymic Injection of Donor Bore Mawow Cells" Transplantation Proceedings. 27. 1607-1608 (1995)
