ECDI-fixed allogeneic splenocytes induce donor-specific tolerance for long-term survival of islet transplants via two distinct mechanisms.
Journal Article (Journal Article)
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 beta 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.
Full Text
Duke Authors
Cited Authors
- Luo, X; Pothoven, KL; McCarthy, D; DeGutes, M; Martin, A; Getts, DR; Xia, G; He, J; Zhang, X; Kaufman, DB; Miller, SD
Published Date
- September 23, 2008
Published In
Volume / Issue
- 105 / 38
Start / End Page
- 14527 - 14532
PubMed ID
- 18796615
Pubmed Central ID
- PMC2567158
Electronic International Standard Serial Number (EISSN)
- 1091-6490
Digital Object Identifier (DOI)
- 10.1073/pnas.0805204105
Language
- eng
Conference Location
- United States