Long‐Term Lung Transplantation in Nonhuman Primates. Issue 5 (13th March 2015)

• Record Type: Journal Article
• Authors: Aoyama, A.; Tonsho, M.; Ng, C. Y.; Lee, S.; Millington, T.; Nadazdin, O.; Wain, J. C.; Cosimi, A. B.; Sachs, D. H.; Smith, R. N.; Colvin, R. B.; Kawai, T.; Madsen, J. C.; Benichou, G.; Allan, J. S.
• Is Part Of: American journal of transplantation. Volume 15:Issue 5(2015:May)
• Page Start: 1415
• Page End: 1420
• Publication Date: 2015-03-13
• Subjects: basic (laboratory) research/science -- lung transplantation/pulmonology -- animal models: nonhuman primate -- immunosuppressant -- fusion proteins and monoclonal antibodies -- Immunosuppressant -- polyclonal preparations; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13130
• Languages: English
• ISSNs: 1600-6135

Abstract

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. Abstract : The authors describe a novel nonhuman primate lung transplant model that addresses the high propensity for rejection in these allografts.