| Project/Area Number |
05671019
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
NAKAI Ichiro Kyoto Prefectural University of Medicine Second Department of Surgery, 医学部・第2外科学教室, 助手 (30188867)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | BB rats / graft vs host disease / irradiation / tolerance / pancreas transplantation / islet transplantation / autoimmunity / rejection / 骨髄細胞 |
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| Research Abstract |
Beta cell destruction in human and animal models of IDDM is the result of a chronic autoimmune process. Following successful islet or whole pancreas transplantation in diabetic recipients, recurrent hyperglycemia may result from graft rejection or recurrence of the original beta cell-specific autoimmune process. We investigated the susceptibility of MHC-incompatible islet or whole pancreas transplants to the autoimmune process. Tolerance was achieved by injection of neonatal BB rats (<24hrs old) with 50*10^6 MHC-incompatible Lewis (RT1 : 1) bone marrow cells. Intraportal islet or enteric-drained whole pancreas transplantation from Lewis donors was performed in diabetes-prone tolerant BB rats. Tolerant BB diabetic rats did not reject Lewis pancreas, but they died normo- or hypoglycemic from lethal graft-vs-host deisease. In contrast, nontolertant diabetic BB rats reject naive Lewis grafts. Lewis islets into tolerat BB rats avioded graft-vs-host disease but recurrence of hyperglycemia was observed. Whole pancreas graft donors were irradiated (1200 rad) in vivo 24-48 hrs prior to transplantation, and tolerant BB rats showed recurrent hyperglycemia. With allotolerance eliminating rejection and graft irradiation eliminating graft-vs-host disease, the most plausible explanation for recurrence of hyperglycemia is autoimmunity to beta cells, which then cannot be MHC-restricted. MHC-incompatible whole pancreas may be slightly less vulnerable than MHC-incompatible islets.
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