Mixed hematopoietic chimerism induces long-term tolerance to cardiac allografts in miniature swine

Background. Tolerance to cardiac allografts has not been achieved in large animals using methods that are readily applicable to human recipients. We i nvestigated the effects of mixed hematopoietic chimerism on cardiac allogra ft survival and chronic rejection in miniature swine Methods. Recipients were T-cell depleted using a porcine CD3 immunotoxin, a nd each received either of two nonmyeloablative preparative regimens previo usly demonstrated to permit the establishment of stable mixed hematopoietic chimerism across MHC-matched, minor-antigen-mismatched histocompatibility barriers. Five to 12 months after the chimerism was induced, hearts from th e original cell donors were heterotopically transplanted into the stable mi xed chimeras. Results. Cardiac allografts transplanted into untreated recipients across s imilar minor antigen barriers were rejected within 44 days (within 21, 28, 35, 39, 44 days among individual study subjects). In contrast, hearts trans planted into the mixed chimeras were all accepted long term ( > 153, > 225, > 286, > 362 days) without immunosuppressive drugs and developed minimal v asculopathy. Conclusions. Mixed hematopoietic chimerism, established in miniature swine using clinically relevant, nonmyeloablative conditioning regimens, permits long-term cardiac allograft survival without chronic immunosuppressive ther apy, significant vasculopathy, or graft-versus-host disease. (Ann Thorac Su rg 2000; 70:131-9) (C) 2000 by The Society of Thoracic Surgeons.