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; T. Kawai; D. H. Sachs; G. Benichou; J. F. Markmann

doi:10.1111/ajt.13329

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. YehT. Kawai, D. H. Sachs, G. Benichou, J. F. Markmann

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26 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 language	English
Pages (from-to)	2739-2749
Number of pages	11
Journal	American Journal of Transplantation
Volume	15
Issue number	10
DOIs	https://doi.org/10.1111/ajt.13329
Publication status	Published - 2015 Oct 1
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Immunology and Allergy
Transplantation
Pharmacology (medical)

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10.1111/ajt.13329

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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., ... Markmann, J. F. (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, 15(10), 2739-2749. https://doi.org/10.1111/ajt.13329

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

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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.",

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AU - Cappetta, K.

AU - Nadazdin, O. M.

AU - Yamada, Y.

AU - Yeh, H.

AU - Kawai, T.

AU - Sachs, D. H.

AU - Benichou, G.

AU - Markmann, J. F.

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

Abstract

Keywords

ASJC Scopus subject areas

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