374: Thymectomy does not abrogate long-term acceptance of MHC class I-disparate lung allografts

Abstract

Background— We have previously reported that tolerance to class I disparate lung allografts in miniature swine could be induced using an intensive 12-day course of tacrolimus and that pretransplant sensitization with immunogenic MHC class I allopeptides failed to block the induction of tolerance. We also have previously reported the importance of the presence of the thymus in the induction of tolerance to isolated heart, kidney, and combined heart-kidney transplants. In this study, we examined the impact of thymectomy on tolerance induction. Methods— Orthotopic left lung transplantation was performed using MHC class I-disparate donors. The recipients received a 12-day course of high-dose tacrolimus (n = 6). Total thymectomies were performed in three of the swine, 21 days prior to transplantation. Lung grafts were monitored by chest radiography and serial open lung biopsy. Results— All euthymic recipients maintained their grafts over one year. None of the thymectomized recipients has shown graft loss in the six to ten months following transplantation. Although isolated lesions of obliterative bronchiolitis (OB) were occasionally seen in one thymectomized animal on biopsy, donor-specific unresponsiveness has been observed on assays of cell-mediated lymphocytotoxicity (CML) in all recipients. Moreover, co-culture CML assays have shown that recipient lymphocytes can strongly inhibit the normally robust response of naive recipient-matched lymphocytes to donor antigen. This inhibition was not seen when using stimulators primed with thirdparty antigens against appropriate targets. Conclusions— These data suggest that thymus-independent peripheral regulatory mechanisms may be sufficient to induce and maintain long-term acceptance of the lung allografts. 5 Address correspondence to: James S. Allan, MD, Massachusetts General Hospital, Blake 1570, 55 Fruit Street, Boston, MA 02114., Phone: 978-745-1581, Fax: 978-745-9024, E-mail: jallan@partners.org. 1This work was supported in part by grants from the Thoracic Surgery Foundation for Research and Education (Sahara/Allan), the International Society for Heart and Lung Transplantation (Shoji), the American Surgical Association Foundation (Allan), and the National Institutes of Health 1RO1-HL67110-01-A1 (Allan). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Transplant Proc. Author manuscript; available in PMC 2007 July 15. Published in final edited form as: Transplant Proc. 2006 December ; 38(10): 3253–3255. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript