| Project/Area Number |
07457263
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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 | Fujita Health University |
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Principal Investigator |
SUGIOKA Atsushi Fujita Health Univ., Dept.of Surgery, instructor, 医学部・外科学(II), 講師 (20171150)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Miwa Fujita Health Univ., Dept.of Surgery, researcher, 医学部, 研究員
林 収 ひまわり検診センター, 所長
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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 |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1995: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | immunological tolerance / liver transplantation / mouse / MHC / microchimerism / RT-PCR / Flowcytometry / soluble MHC class I antigen / 共焦点レーザー顕微鏡 |
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| Research Abstract |
To establish the the way to induce immunological tolerance, which means specific non-immunoreactive state to the donor antigen, is the final subject for organ transplantation. Liver transplantation is well known for the unique ability to induce tolerance. However, it is inevitable to establish the orthotopic liver transplantation in the mouse (OMLT) in order to elucidate the molecular mechanism inducing tolerance. The purposes of this study are to establish OMLT and to clarify the molecular mechanism of inducing tolerance.
Although OMLT had been reported from only one institute in the world, we established OMLT using our modified technique. We began OMLT from August 1994 and have performed 915 cases until March 1997 with the success rate being 97%.
Among 48 allocombinations of OMLTs using II inbred strains, graft acceptance and tolerance induction were obtained without an exception. Furthermore, these phenomena were also obscrved in OMLTs using wild mice whose genetic background were com
… More
pletely different from laboratory ones. Thus, it is assured that graft acceptance and tolerance induction in OMLTs are general phenomena and that OMLT is the optimal model for investigation of the mechanism of tolerance induction.
First, we in vestigated the significance of microchimerism, whch was advocated for the cause of tolerance by Starzl, using confocal laser microscopy and RT-PCR.Although microchimerism was identified until 2 to 3 weeks after OMLT,it disappeared afterwards, which indicated that microchimerism was the consequence rather than the cause of tolerance.
Flowcytometry revealed the existence of the double-positive cells which expressed both MHC class I antigen for donor and recipient in the grafted liver. Analyzes of surface antigens showed the double-positive cells possessed the characteristics of the premature dendritic cells of the recipient origin. RT-PCR using specific primers for soluble MHC class I antigen dcmonstrated that it was constantly generated in the grafted liver. These data suggests that the double-positive cells were possibly the recipint type premature dendritic cells which trapped the donor type soluble MHC class I antigen to their surface.
In conclusi On, it was revealed that tolerance is not induced by microchimerism but by interaction between specific cells and soluble MHC class I antigens generated in the grafted liver. Less
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