| Project/Area Number |
09671238
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | KUMAMOTO UNIVERSITY |
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Principal Investigator |
YAMAGUCHI Yasuo Kumamoto University, School of Medicine, Associate Professor, 医学部, 助教授 (90253757)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Katsutaka Kumamoto University, College of Medical Science, Professor, 医療技術短期大学部, 教授 (10040213)
OGAWA Michio Kumamoto University, School of Medicine, Professor, 医学部, 教授 (30028691)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | CD8-POSITIVE T CELL / PHENOTYPE / CD45RC / EXTRATHYMIC DIFFERENTIATION / LIVER TRANSPLANTATION / TGF-beta / RAT / IMMUNOLOGIC UNRESPONSIVENESS / liver fransplantation / DST / CD4^+T cell / CD8^+T cell / IL-10 / IL-18 |
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| Research Abstract |
A single intravenous injection of freshly heparinized donor-specific blood (DST) prior to transplantation significantly prolonged the survival of fully allogeneic ACI(RT1^a)-to-LEW(RT1^l) rat hepatic allografts. Additionally, pretreatment of LEW rats with PVG.r1 blood, which shares only the RT1. A major histocompatibility complex (MHC) region with ACI, significantly prolonged the survival of ACI hepatic allografts. We report the cellular identity of hepatic allograft leukocyte infiltrates following transplantation.
Fluorescence-activated cell sorting (FACS) analysis revealed that CD8^+ T cells infiltrating liver allografts could be divided into two subsets, CD45RC^-CD8^+ and CD45RC^+CD8^+ T cells, and that the ratio of CD4SRC^-CD8^+ T cells/ CD45RC^+CD8^+ T cells was significantly higher in hepatic allografta of recipients pretreated with DST as compared to untreated allografts. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that CD4SRC^+CD8^+ T cells harvest
… More
ed from untreated hepatic allografts expressed interleukin (IL)-2 and interferon (IFN)-gamma. In contrast, CD45RC^-CD8^+ T cells from hepatic allografts pretreated with DST expressed IL-4 and IL-1O, but not IL-2. These results indicated that the CD45RC leukocyte common antigen could be used to differentiate CD8^+ T cells following pretreatment with DST.Persistent infiltration of CD4SRC^-CD8^+ T cells, capable of secreting Th2-type cytokines may prevent allograft rejection by causing immunologic unresponsiveness. I addition, the ratio of CD45RC^-CD8^+ T cells/CD45RC^+CD8^+ T cells was significantly higher in hepatic allografts of recipients pretreated with PVO.rl blood compared to untreated allografts.
The levels of IEN-gamma, IL-12, and IL-18 mRNA in untreated hepatic allografts were significantly higher than those observed in allografts from recipients pretreated with DST.Transforming growth factor (TGF)-beta and IL-1O mRNA levels in grafts of transfused animals were significantly greater than those in the untreated allograft group. IL-12 and IL-18 mRNA transcripts in an allogeneic mixed lymphocyte reaction were inhibited by IL-10 and TGF-beta. CD4SRC expression was significantly inhibited by TGF-beta, but not IL-1O.
Thus CD45RC^-CD8^+T cells expressed IL-4 and IL-1O mRNA and induced by TGF-beta may play an important role in immunologic unresponsiveness induced by donor antigens prior to transplantation. Less
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