1996 Fiscal Year Final Research Report Summary
Study of Renal Transplantation by a New Immunosuppressive Method
| Project/Area Number |
06304038
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 総合 |
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| Research Field |
Urology
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| Research Institution | Kinki University |
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Principal Investigator |
KURITA Takashi Department of Urology, Kinki University School of Medicine, Prof., 医学部, 教授 (10088528)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIDONO Sadao Department of Urology, Koube University School of Medicine, Prof., 医学部, 教授 (30030935)
KAWABE Kazuki Department of Urology, Tokyo University School of Medicine, Prof., 医学部, 教授 (20124670)
OKUYAMA Akihiko Department of Urology, Osaka University School of Medicine, Prof., 医学部, 教授 (20093388)
TOHMA Hiroshi Department of Urology, Tokyo Women's Medical college, Prof., 教授 (90075549)
KOSHIBA Ken Department of Urology, Kitazato University School of Medicine, Prof., 医学部, 教授 (40050380)
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| Project Period (FY) |
1994 – 1996
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| Keywords | T-cell associated cytokines / rat kidney transplantation / lymphocyte activation signal / microchimerism / FK506 / FTY720 / HGF |
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| Research Abstract |
Induction of tolerance by transferrance of chemically modified alloantigens was reported last year. To analyze this mechanism, we examined T-cell associated cytokines within renal allografts in the tolerance model by RT-PCR.No expression of cytokines of mRNAs was observed in isografts. In contrast, allografts demonstrated expression of both Th1 (IL-2, gamma-INF) and Th2 (IL-4, IL-10) associated cytokines mRNAs. In addition, the expression of IL-2 mRNA in treated allografts was low compared with taht in untreated ones. This results suggested that induction of tolerance may be responsible for immunoredirection of Th1/Th2 function in allografts. Recently, a novel immunosuppressive agent, FTY720 is explored. We studied the immunosuppressive effect and mechanism of FTY720. This agent induced dramatic decrease of peripheral lymphocytes in native rats while other leukocytes showed no significant changes. Enhancement of renal allograft survival was observed by oral administration of FTY720. In
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terestingly, pretreatment with FTY720 was more effective than posttransplant administration. Detection for apoptosis was tried because we found atrophic spleens in long-term survival rats receiving FTY720. No apoptosis was detected in spleens of FTY720-treated transplanted rats. Thereafter, production Th1 associated cytokines was examined in spleens during rejection (posttransplant day 5). We detected IL-2 mRNA in spleens of untreated transplanted rats by RT-PCR.However, no expression of this mRNA in spleens of treated transplanted rats with FTY720. We speculated that long-term survival rats may require functional change of spleens. In the clinical study, serial biopsies of renal grafts and pharmacokinetics study of FK506 were carried out in patients receiving FK506. We emphasized the immportance of monitoring blood concentration of FK506. Frequent measurements should be carried out to decrease renal toxicity induced by FK506. On the other hand, we analyzed the microchimerism in blood and skin of recipients compared with MLR response. Microchimerism dose not seem to be associated with index of MLR response after transplantation. Further study is necessary to confirm this results. For monitoring rejection, HGE of blood was measured in recipients. Blood HGF had a trend to elevate during rejection. We are in progress in investigating the localization of HGF within rejected allografts by immunostaining. Less
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