Long-term lung transplantation in nonhuman primates

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
A AoyamaJ S Allan

Abstract

Despite advances in surgical technique and clinical care, lung transplantation still remains a short-term solution for the treatment of end-stage lung disease. To date, there has been limited experience in experimental lung transplantation using nonhuman primate models. Therefore, we have endeavored to develop a long-term, nonhuman primate model of orthotopic lung transplantation for the ultimate purpose of designing protocols to induce tolerance of lung grafts. Here, we report our initial results in developing this model and our observation that the nonhuman primate lung is particularly prone to rejection. This propensity toward rejection may be a consequence of 1) upregulated nonspecific inflammation, and 2) a larger number of pre-existing alloreactive memory T cells, leading to augmented deleterious immune responses. Our data show that triple-drug immunosuppression mimicking clinical practice is not sufficient to prevent acute rejection in nonhuman primate lung transplantation. The addition of horse-derived anti-thymocyte globulin and a monoclonal antibody to the IL-6 receptor allowed six out of six lung recipients to be free of rejection for over 120 days.

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Citations

Apr 24, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M TonshoJ S Allan
Nov 26, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M AvsarG Warnecke
Jul 23, 2016·JCI Insight·Kiyohiko HottaTatsuo Kawai
Nov 27, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M Nicosia, A Valujskikh
Apr 4, 2017·Clinical and Experimental Immunology·T OuraT Kawai
Aug 4, 2018·Nature Protocols·Andrea MariscalShaf Keshavjee
Mar 22, 2019·Transplantation·Franka MessnerGerald Brandacher
Jul 12, 2019·Science Translational Medicine·Stuart J KnechtleJoren C Madsen
Feb 11, 2020·Transplantation·Michael NicosiaAnna Valujskikh
Sep 26, 2017·Annals of the American Thoracic Society·David H Sachs
Feb 5, 2021·Clinical & Translational Immunology·Peter RiddellStephen C Juvet
Mar 14, 2021·Seminars in Thoracic and Cardiovascular Surgery·Kentaro KitanoHarald C Ott

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