The effect of thymectomy on tolerance induction and cardiac allograft vasculopathy in a miniature swine heart/kidney transplantation model

Background We have previously demonstrated that MHC class I disparate heart s transplanted into miniature swine treated with a short course of cyclospo rine developed florid cardiac allograft vasculopathy (CAV) and were rejecte d within 55 days. However, when a donor-specific kidney is cotransplanted w ith the heart allograft, recipients become tolerant to donor antigen and ac cept both allografts long-term without the development of CAV, In the prese nt study, we have investigated the role of the host thymus in the induction of tolerance and prevention of CAV in heart/kidney recipients. Methods. Total thymectomies were performed in six animals (postoperative da y [POD]-21), which on day 0 received either an isolated MHC class I dispara te heart allograft (n=3) or combined class I disparate heart and kidney all ografts (n=3), followed in both cases by a 12-day course of cyclosporine (P OD 0-11). Graft survival and the development of CAV in these thymectomized recipients were compared to the same parameters in non-thymectomized, cyclo sporine-treated recipients bearing either class I disparate heart allograft s (n=5) or heart and kidney allografts (n=4), Results. In the group of animals bearing isolated class I disparate heart a llografts, the thymectomized recipients rejected their allografts earlier ( POD 8, 22, 27) than the non-thymectomized recipients (POD 33,35,45,47,55). The donor hearts in both the thymectomized and non-thymectomized animals de veloped florid CAV, In the group of animals bearing combined class I dispar ate heart and kidney allografts, the non-thymectomized recipients accepted both donor organs long term with no evidence of CAV, In contrast, none of t he thymectomized heart/kidney recipients survived >100 days, and they all d eveloped the intimal proliferation of CAV, Conclusion. Thymic-dependent mechanisms are necessary for the induction of acquired tolerance and prevention of CAV in porcine heart/kidney recipients .