Date: Saturday, May 2, 2015
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Exhibit Hall E
Background: We have previously shown that tolerance of heart allografts across a full MHC barrier can be induced in miniature swine after a 12-day course of high-dose tacrolimus by donor kidney co-transplantation. This same high-dose immunosuppression is also capable of inducing tolerance of full MHC-mismatched lung allografts. To determine the element responsible for kidney-induced cardiac allograft tolerance, we investigated whether a common factor between lung and kidney allografts would allow lung co-transplantation to induce tolerance of cardiac allografts.
Methods: Heart plus kidney allografts (n=3) or heart plus lung allografts (n=3) were transplanted into full MHC-mismatched recipients treated with high-dose tacrolimus for 12 days. Serial biopsies were performed to evaluate for rejection and in vitro assays were performed detect the state of donor-responsiveness.
Results: Animals who received heart plus kidney allografts demonstrated long-term survival of both heart and kidney allografts for >200 days without evidence of rejection on serial biopsies. Heart plus kidney recipients demonstrated loss of donor-specific responsiveness in CML and MLR assays, were free of alloantibody, and showed prolonged survival of donor skin grafts. Two heart plus lung recipients demonstrated long-term survival of both heart and lung allografts for >152 days and >46 days, loss of donor-specific responsiveness by CML by postoperative day 30, and no alloantibody production. One heart plus lung recipient rejected both heart and lung allografts by day 41; this was accompanied by re-establishment of anti-donor responsiveness on MLR and production of IgG alloantibody.
Conclusion: To our knowledge, this is the first study showing that lung co-transplantation is able to induce tolerance of cardiac allografts across a full MHC mismatch, similar to kidney co-transplantation. Interestingly, one heart plus lung recipient showed rejection of both heart and lung allografts, suggesting that the barrier for cardiac tolerance via lung co-transplantation is higher than for kidney co-transplantation. Future work will determine what shared elements between lung and kidney grafts promote cardiac allograft tolerance.
To cite this abstract in AMA style:Madariaga M, Spencer P, Michel S, II GLaMuraglia, O'Neil M, Mannon E, Leblang C, Rosales I, Colvin R, Sachs D, Allan J, Madsen J. Effects of Heart and Lung Co-Transplantation Across a Full MHC Barrier in Miniature Swine [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/effects-of-heart-and-lung-co-transplantation-across-a-full-mhc-barrier-in-miniature-swine/. Accessed April 5, 2020.
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