| Project/Area Number |
16591262
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
SUGITANI Atsushi (2005) Kyushu University, Faculty of Medicine, Associate Professor, 大学病院, 講師 (00294934)
本山 健太郎 (2004) 九州大学, 大学院・医学研究院, 助手 (40315198)
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| Co-Investigator(Kenkyū-buntansha) |
KATANO Mitsuo Kyushu University, Faculty of Medicine, Professor, 大学院・医学研究院, 教授 (10145203)
杉谷 篤 九州大学, 大学病院, 講師 (00294934)
山元 啓文 九州大学, 大学病院, 助手
大田 守仁 九州大学, 大学病院, 医員
吉田 淳一 九州大学, 大学病院, 医員
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | regulatory T cell / transplantation tolerance / pancreas transplantation / spleen |
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| Research Abstract |
Aim : To investigate the role of spleen and regulatory T cell for pancreas transplantation.
Method : After induction of diabetes mellitus by streptozotocin, spleen and/or pancreaticoduodenal transplantation (S/PTx or PTx) into the peritoneal cavity was performed using a modification of Lee's method. Graft survival was compared in isograft (Lew to Lew), allograft (DA to Lew) and allograft with tacrolimus induction (1mg/kg/day for 4days) groups. The rate of CD25+CD4+ T cell and the Foxp3 expression in peripheral blood (PB), recipient spleen (RS) and donor spleen (DS) were examined using Flowcytometry and RT-PCR, respectively. The specimen was obtained from RS, DS, and graft pancreas for histological examination on day7.
Results : Isotransplanted S/PTx (n=4) and PTx (n=4) were both survived longer than 100days. Both allotransplanted S/PTx (n=6) and PTx (n=6) without tacrolimus rejected the graft on 12.3±2.7d, 11.7±2.9d, respectively. S/PTx (n=6) with tacrolimus survived for 22.8±7.9d, and PTx (n=6) with tacrolimus survived for 13.5±3.7d (p=0.0069). Rejected S/PTx grafts (n=5) showed that 1)CD25+CD4+T cells were dominant in PB, RS and DS, 2) Donor derived CD25+CD4+T cells disappeared after 7days. Survived S/PTx grafts (n=5) showed that 1)donor CD25+CD4+T cells remained in PB, RS and DS over 7days, 2)the rate of Foxp3 expression was in both RS and DS on day7 compared with Rejected graft (p=0.028). There were more lymphocyte infiltration and reduction in white pulp in RS and DS.
Conclusion : The pancreas graft survived longer by combined spleen transplantation and a short course of calcineurin inhibitor. Donor derived regulatory T cells (Foxp3 and CD25/4 cells) existing in both recipient and donor spleen would lead micro-chimerism and prolonged survival.
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