1999 Fiscal Year Final Research Report Summary
Prolongation of renal transplant survival by the management of lymphocyte homing
| Project/Area Number |
10671504
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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 |
Urology
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| Research Institution | Kinki University |
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Principal Investigator |
KUNIKATA Seiji Kinki University of Medicine, Assistant Professor, 医学部・附属病院, 助教授 (80150811)
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| Project Period (FY) |
1998 – 1999
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| Keywords | FTY720 / rat kidney transplantation / lymphocytes / homing |
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| Research Abstract |
This study was undertaken to investigate the effect and immunosuppressive mechanism of a novel drug, FTY720 for prolongation of renal allografts in a rat model. Using a BN to LEW rat combination, significant enhancement of allograft survival was observed by administration of FTY720. Interestingly, rats given only twice before grafting had longer survival significantly than these receiving posttransplant treatment. However, FTY720 induced no change in MLR response. This agent induced dramatic decrease of peripheral CD4 and CD8 lymphocytes after the administration. Spleens and lymphocytes of transplanted rats under immunosuppression of FTY720 showed no apoptosis. Infiltrating lymphocytes decreased within renal grafts receiving FTY720 while lymphocytes of lymphnodes increased. Expression of IL-2 mRNA within allografts treated with FTY720 was low compared with that within untreated allografts by RT-PCR study. No IL-2 production was observed within spleens of treated rats. FTY720 induced no change in homing receptors, L-selectin and E-selectin of lymphocytes. Homing or migration of lymphocytes to lymphonodes induces the decrease of infiltrating lymphocytes and T-cell associated cytokines in renal allografts of treated with FTY720. Sequently, this immunosuppressive action leads the prolomgation of renal allografts survival.
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