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

2015; Elsevier BV; Volume: 15; Issue: 10 Linguagem: Inglês

10.1111/ajt.13329

1600-6143

Ji Lei, Jessica Kim, Shuai Shi, X. Zhang, Zurab Machaidze, S. Lee, Christian Schuetz, Paulo N. Martins, Tetsu Oura, Evan A. Farkash, Ivy A. Rosales, R. Neal Smith, Ryan Stott, K.M. Lee, Julie Soohoo, S Bosković, K. Cappetta, O. Nadazdin, Yohei Yamada, Heidi Yeh, Tatsuo Kawai, David H. Sachs, Gilles Bénichou, James F. Markmann,

Diabetes and associated disorders

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.