ECDI-fixed allogeneic splenocytes induce donor-specific tolerance for long-term survival of islet transplants via two distinct mechanisms

Xunrong Luo*, Kathryn L. Pothoven, Derrick McCarthy, Mathew DeGutes, Aaron Martin, Daniel R. Getts, Guliang Xia, Jie He, Xiaomin Zhang, Dixon B. Kaufman, Stephen D. Miller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)14527-14532
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number38
DOIs
StatePublished - Sep 23 2008

Keywords

  • Anergy
  • Islet transplantation
  • Programmed death-1
  • Regulatory T cells
  • Transplantation

ASJC Scopus subject areas

  • General

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