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Thymectomy does not abrogate long-term acceptance of MHC class I-disparate lung allografts in miniature Swine.

Abstract：

UNLABELLED: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 in lung transplantation. 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 for over 1 year. None of the thymectomized recipients has experienced graft loss in the 6 to 10 months following transplantation. Although isolated lesions of obliterative bronchiolitis were occasionally seen in one thymectomized animal on biopsy, donor-specific unresponsiveness has been observed on assays of cell-mediated lymphocytotoxicity in all recipients. Moreover, co-culture assays have shown that recipient lymphocytes can strongly inhibit the normally robust response of naïve recipient-matched lymphocytes to donor antigen. This inhibition was not seen when using stimulators primed with third-party 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.

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Sahara H,Weiss MJ,Ng CY,Houser SL,Pujara AC,Sayre JK,Wain JC,Sachs DH,Madsen JC,Allan JS

doi

10.1016/j.transproceed.2006.10.064

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

3253-5

issue

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(06)01293-0

journal_volume

pub_type

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Thymectomy does not abrogate long-term acceptance of MHC class I-disparate lung allografts in miniature Swine.