| Project/Area Number |
14370367
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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 | National Research Institute for Child Health and Development |
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Principal Investigator |
LI X-k. Natl.Res.Inst.For Child Health. & Dev., Dept.of Innovative Surgery, Lab Head, 移植・外科研究部, 室長 (60321890)
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| Co-Investigator(Kenkyū-buntansha) |
FUNESHINA N. Natl.Res.Inst.For Child Health. & Dev., Dept.of Surgical Research, Researcher, 共同研究管理室, 流動研究員 (60399483)
UEMOTO S. Mie University School of Medicine, Dept.of Surgery, Professor, 医学部・第一外科講座, 教授 (40252449)
鈴木 英年 浜松医科大学, 第一外科講座, 研究生 (70242758)
FUJINO M. Natl.Inst.of Infectious Disease, AIDS Res.Ctr, Researcher, エイズ研究センター・第二研究グループ, 研究員 (50392329)
SUZUKI H. Hamamatus University School of Medicine, Dept.of Surgery, Asst.Professor
鈴木 盛一 国立成育医療センター研究所, 移植・外科研究部, 部長 (00111386)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | transplantation immunology / tolerance / regulatory cell / gene / co-stimulatory / DNA chip / 臓器移植 / allograft / isograft |
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| Research Abstract |
Induction of transplant tolerance to allogeneic donor grafts is a clinically desirable goal, and ongoing research underscores the need for new scientific inquiry. In an effort to provide unbiased insight into transplant tolerance, we took an approach involving gene expression profiling in peripheral blood mononuclear cells from Tacrolimus (FK506) induced tolerance of the fully mismatched liver allograft rat and the recipients of living-donor liver transplants(LDLT) who had retained an immune tolerance with a well-functioning graft for several years. First, we compared mRNA profiles in PBL from tolerant recipients with those from syngeneic recipients using a DNA microarray with probe sets corresponding to more than 8000 rat genes. There were 96 up-regulated and 103 down-regulated genes in the tolerant recipients. In the up-regulated group, there were 76 known genes and 20 expressed sequence tags(ESTs). In the down-regulated groups, there were 87 known genes and 16 ESTs. Our data indicat
… More
ed that FK506 treatment induced tolerance and expansion of regulatory cells and the DNA microarray technology was useful for this application and provided many informative insights into the mechanism of lymphocyte regulation. Second, employing comparative analyses with non-transplanted normal healthy volunteers, we demonstrated that the majority of reliable detected genes were similar, implying a steady state between the two groups and allowing us to define a set of tolerant signature genes. We determined that 5.6% of the genes in the tested genome (of which 627 up-regulated and 90 down-regulated) were significantly regulated and specific to tolerant LDLT recipients, indicating a significant genetic feature for inducing and maintaining immune tolerance. Notably, both gene-related immune response and cell membrane were shown to have distinct transcript categorized profiles. Moreover, the expression of several selected genes was confirmed by semi-quantitative RT-PCR, which correlated to microarray data. Our data indicated that cDNA microarray technology was useful for this application and provided many informative insights into transplant tolerance mechanisms. Less
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