Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 38, Pages 14527-14532Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0805204105
Keywords
anergy; programmed death-1; regulatory T cells; transplantation; islet transplantation
Categories
Funding
- Juvenile Diabetes Research Foundation [1-2007-1055]
- National Institutes of Health [NS-026543, K08 DK-070029]
- National Multiple Sclerosis Society [RG 3965-A-8]
- Myelin Repair Foundation
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A major challenge for human allogeneic islet transplantation is the development of effective methods to induce donor-specific tolerance to obviate the need for life-long immunosuppression that is toxic to the insulin-producing 13 cells and detrimental to the host. We developed an efficient donor-specific tolerance therapy that utilizes infusions of ethylene carbodiimide (ECDI)-treated donor splenic antigen-presenting cells that results in indefinite survival of allogeneic islet grafts in the absence of immunosuppression. Furthermore, we show that induction of tolerance is critically dependent on synergistic effects between an intact programmed death 1 receptor-programmed death ligand 1 signaling pathway and CD4(+)CD25(+) Foxp3(+) regulatory T cells. This highly efficient antigen-specific therapy with a complete avoidance of immunosuppression has significant therapeutic potential in human islet cell transplantation.
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