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

J. Lei, J. I. Kim, S. Shi, X. Zhang, Z. Machaidze, S. Lee, C. Schuetz, P. N. Martins, T. Oura, E. A. Farkash, I. A. Rosales, R. N. Smith, R. Stott, K. M. Lee, J. Soohoo, S. Boskovic, K. Cappetta, O. M. Nadazdin, Y. Yamada, H. Yeh & 4 others T. Kawai, D. H. Sachs, G. Benichou, J. F. Markmann

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2739-2749
Number of pages11
JournalAmerican Journal of Transplantation
Volume15
Issue number10
DOIs
Publication statusPublished - 2015 Oct 1
Externally publishedYes

Fingerprint

Graft Survival
Regulatory T-Lymphocytes
Immunosuppression
Primates
Antigens
Ethyldimethylaminopropyl Carbodiimide
Interleukin-6 Receptors
Isoantibodies
Islets of Langerhans Transplantation
Sirolimus
Immunotherapy
Maintenance
Lymphocytes
T-Lymphocytes
Antibodies

Keywords

  • Donor-specific hyporesponsiveness
  • donor-specific transfusion/antigen delivery
  • graft survival
  • tolerance
  • tolerance: depletion

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Pilot Study Evaluating Regulatory T Cell-Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model. / Lei, J.; Kim, J. I.; Shi, S.; Zhang, X.; Machaidze, Z.; Lee, S.; Schuetz, C.; Martins, P. N.; Oura, T.; Farkash, E. A.; Rosales, I. A.; Smith, R. N.; Stott, R.; Lee, K. M.; Soohoo, J.; Boskovic, S.; Cappetta, K.; Nadazdin, O. M.; Yamada, Y.; Yeh, H.; Kawai, T.; Sachs, D. H.; Benichou, G.; Markmann, J. F.

In: American Journal of Transplantation, Vol. 15, No. 10, 01.10.2015, p. 2739-2749.

Research output: Contribution to journalArticle

Lei, J, Kim, JI, Shi, S, Zhang, X, Machaidze, Z, Lee, S, Schuetz, C, Martins, PN, Oura, T, Farkash, EA, Rosales, IA, Smith, RN, Stott, R, Lee, KM, Soohoo, J, Boskovic, S, Cappetta, K, Nadazdin, OM, Yamada, Y, Yeh, H, Kawai, T, Sachs, DH, Benichou, G & Markmann, JF 2015, 'Pilot Study Evaluating Regulatory T Cell-Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model', American Journal of Transplantation, vol. 15, no. 10, pp. 2739-2749. https://doi.org/10.1111/ajt.13329
Lei, J. ; Kim, J. I. ; Shi, S. ; Zhang, X. ; Machaidze, Z. ; Lee, S. ; Schuetz, C. ; Martins, P. N. ; Oura, T. ; Farkash, E. A. ; Rosales, I. A. ; Smith, R. N. ; Stott, R. ; Lee, K. M. ; Soohoo, J. ; Boskovic, S. ; Cappetta, K. ; Nadazdin, O. M. ; Yamada, Y. ; Yeh, H. ; Kawai, T. ; Sachs, D. H. ; Benichou, G. ; Markmann, J. F. / Pilot Study Evaluating Regulatory T Cell-Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model. In: American Journal of Transplantation. 2015 ; Vol. 15, No. 10. pp. 2739-2749.
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