A Trial to Obtain a Donor-Specific Immunotorelance Using a Vascularized Thymus Allograft after Host Thymectomy and Host Lymphocyte Depletion
| Project/Area Number |
11671153
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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 | Saitama Cancer Center |
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Principal Investigator |
NISHIMURA Yoji Saitama Cancer Center, Department of Abdominal Surgery, Researcher, 腹部外科, 研究員 (10218208)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | thymus transplantation / immunotorelance / vascularized thymus / anti-CDS antibody / host thymectomy / FK506 / ALS |
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| Research Abstract |
There sometimes occurs spontaneous immunotorelance in clinical organ transplantation, however, intentional induction of immunotorelance in clinical setting has not been reported successful yet. We developed the technique of whole-organ thymus-heart composite grafting into the host abdominal cavity and reported the positive effect of the thymus allograft for the simultaneously transplanted heart allograft survival. By adding the host thymectomy and splenectomy and giving ALS and anti-CD3 antibody, new T lymphocyte which is educated by the thymus allograft can theoretically introduce donor- specific immunotorelance. Our preliminary study showed the safe prolongation of the heart allograft survival without GVHD, but not the immunotorelance, maybe because of the incomplete depletion of the mature host T Iymphocyies. So we planned more complete depletion of the host T Iymphocytes before transplantation. DA to Lewis rats combination or BN to Lewis rats combination was used for whole-organ th
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ymus-heart composite grafting. A week before transplantation host thymectomy was performed and on the day of transplantation host splenectomy was done together with transplantation. Either ALS Iml/body or anti-CD3 antibody 0.15mg/kg was injected intramuscularly twice before transplantation and FK506 was given consecutively for 10 days posttransplantation. Group 3 in which DA to Lewis combination (high responder combination) was chosen
and both ALS and anti-CD3 were given showed a substantial prolongation of the heart allograft survival of the average 84.2 days posttransplantation, but not the immunotorelance. In Group 6 in which BN to Lewis combination (low responder combination) was chosen and both ALS and anti-CD3 were given, all the heart allograft survived more than io days, showed the probable immunotorelance. There was no GVHD in each Group. In conclusion, in the low responder combination of the rats, host thymectomy and splenectomy, together with ALS and anti-CD3 antibody inj$tion, and thymus allografting can safely introduce immunotorelance. Less
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Report
(3 results)
Research Products
(2 results)
