Pilot Study Evaluating Regulatory T Cell-Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model

Am J Transplant. 2015 Oct;15(10):2739-49. doi: 10.1111/ajt.13329. Epub 2015 May 26.

Abstract

The full potential of islet transplantation will only be realized through the development of tolerogenic regimens that obviate the need for maintenance immunosuppression. Here, we report an immunotherapy regimen that combines 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI)-treated donor lymphoid cell infusion (ECDI-DLI) with thymoglobulin, anti-interleukin-6 receptor antibody and rapamycin to achieve prolonged allogeneic islet graft survival in a nonhuman primate (NHP) model. Prolonged graft survival is associated with Treg expansion, donor-specific T cell hyporesponsiveness and a transient absence of donor-specific alloantibody production during the period of graft survival. This regimen shows promise for clinical translation.

Keywords: Donor-specific hyporesponsiveness; donor-specific transfusion/antigen delivery; graft survival; tolerance; tolerance: depletion.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Therapy, Combination
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / immunology*
  • Immunosuppressive Agents / therapeutic use*
  • Islets of Langerhans Transplantation / immunology*
  • Isoantigens / immunology*
  • Lymphocyte Transfusion / methods*
  • Pilot Projects
  • Primates
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Immunosuppressive Agents
  • Isoantigens