An important goal in the treatment of insulin-dependent diabetes by pancreatic islet transplantation is the development of strategies that allow permanent survival of islet allografts without continuous host immunosuppression. In this study, we demonstrate that inoculation of allogeneic bone marrow into the thymus of adult rats treated with a single dose of anti-lymphocyte serum induces an unresponsive state that permits survival of subsequent pancreatic islet allografts transplanted to an extrathymic site. This effect is donor specific, cannot be reproduced by systemic administration of bone marrow, and is associated with persistence of chimeric cells in the thymus of the recipient. In addition, lymph node cells from long-term recipients of intrathymic bone marrow display markedly reduced proliferative responses to donor alloantigens in mixed lymphocyte culture. Interaction of maturing thymocytes with foreign alloantigens may produce the unresponsiveness. This model offers a potential approach for establishing donor-specific allograft acceptance in adult recipients.
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June 01 1992
Promotion of Pancreatic Islet Allograft Survival By Intrathymic Transplantation of Bone Marrow
Andrew M Posselt;
Andrew M Posselt
Department of Surgery, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
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Jon S Odorico;
Jon S Odorico
Department of Surgery, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
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Clyde F Barker;
Clyde F Barker
Department of Surgery, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
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Ali Naji
Ali Naji
Department of Surgery, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
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Address correspondence and reprint requests to Dr. Ali Naji, Hospital of the University of Pennsylvania, Department of Surgery, 3400 Spruce Street, Philadelphia, PA 19104.
Diabetes 1992;41(6):771–775
Article history
Received:
January 01 1992
Revision Received:
January 23 1992
Accepted:
January 23 1992
PubMed:
1534058
Citation
Andrew M Posselt, Jon S Odorico, Clyde F Barker, Ali Naji; Promotion of Pancreatic Islet Allograft Survival By Intrathymic Transplantation of Bone Marrow. Diabetes 1 June 1992; 41 (6): 771–775. https://doi.org/10.2337/diab.41.6.771
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