2005 Fiscal Year Final Research Report Summary
The induction of donor-specific transplantation tolerance in pancreas transplantation combined with spleen in rat
| 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 Kyushu University, Faculty of Medicine, Associate Professor, 大学病院, 講師 (00294934)
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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)
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| Project Period (FY) |
2004 – 2005
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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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[Journal Article] Recurrent nephritic syndrome after living-related renal transplantation resistant to plasma exchange2005
Author(s)
Kohsuke Masutani, Ritsuko Katafuchi, Hirofumi Ikeda, Hirofumi Yamamoto, Kentaro Motoyama, Atsushi Sugitani, Hidetoshi Kanai, Harumitu Kumagai, Hideki Hirakata, Masao Tanaka, Mitsuo Iida
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Journal Title
Clinical Transplantation 19
Pages: 59
Description
「研究成果報告書概要(和文)」より
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