Tolerance Induction of Small Bowel Transplantation Injected by Gene-transferred Donor Dendritic Cells
| Project/Area Number |
12671203
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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 |
Digestive surgery
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
HORI Seiji Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (30312961)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Hideaki Chiba University, University Hospital, Assistant, 医学部・附属病院, 助手 (20292691)
GUNJI Yoshio Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (60241957)
OCHIAI Takenori Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (80114255)
SUZUKI Takao Chiba University, Graduate School of Medicine, Assistant Professor, 大学院・医学研究院, 助教授 (90235961)
HAYASHI Hideki Chiba University, University Hospital, Assistant, 医学部・附属病院, 助手 (20312960)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | small bowel transplantation / Dendritic cell / Gene transfer / CTLA4-Ig / IL10 / Adenovirus / Immunological tolerance / アディノウイルス / アデノウイルスベクター |
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| Research Abstract |
In small bowel transplantation (SBT), the severity of acute rejection has made success difficult. Dendritic cell (DC) has powerful antigen-presenting capacity and acts as an initiator of acute rejection. Thus, it is attractive to use DC for reducing antigen-specific immune responses and for inducing immunological tolerance in SBT.
In this study, we used donor DC which had been transferred CTLA4-Ig or IL10 gene by adenovirus vector (AdCTLA4I-g-DC or AdIL10-DC). SBT was performed by Sonnino's modified method. Briefly, donor mesenteric artery and vein were anastomosed with the recipient's carotid artery and external jugular vein, respectively and Thiry-Vella loop was made on the recipient's neck. DC were prepared as follows. A single cell suspension of splenic cells were cultured for four hours in the culture dish, then, adherent cells were used as DC. CTLA4I-g or IL10 gene was transferred into DC by adenovirus bector, DC were cocultured with AdCTLA4I-g or AdIL10 for four hours. WKAH rat was i.v. presented with 1X10^6DC 7 days before SBT.
The results indicated as follows. The median graft survival time (GST) of F344 small bowel allografts in untreated control WKAH rats was 7 days, which a range of 5-8 days. Presensitization with F344 DC resulted in accerelated rejection, the median GST was 5 days. The median GST in WKAH rat presensitized with AdCTLA4I-g-WKAH-DC or AdIL10-WKAH-DC was 7 day. In contrast, presentation with AdCTLA4I-g-F344-DC or AdIL10-F344-DC resulted in the prolongation of graft survival time, the median GST was 10 days, 9 days, respectively.
The present study demonstrates the imniunosuppressive potency of AdCTLA4-g-DC and AdIL10-DC, but immunological tolerance was not obtained by this method.
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Report
(3 results)
Research Products
(4 results)
