Recipients of MHC class I disparate lung grafts develop T cell reactivity to donor MHC class I allopeptides in an orthotopic swine model

logical reactivity to donor antigens, followed by vascularized heterotopic heart transplantation to determine if CAV still develops in the tolerant recipient. Procedures: In mice, specific immunological nonreactivity was achieved in recipients by (1) neonatal administration of allogeneic spleen cells from F1 donors between class I mismatched donor and recipient strains, (2) acheivement of mixed chimerism by bone marrow infusion of irradiated adult recipients, (3) use of genetically immunodeficient recipients (RAG1-/or SCID). In swine, reduced reactivity was achieved through the induction of mixed chimerism. After nonreactivity was induced and verified through extended persistence of skin grafts, hearts from donors were heterotopically transplanted into the recipients. Results: Most hearts transplanted into tolerant or immunodeficeint mice developed striking vasculopathy in their coronary arteries (neonatal tolerance: 12 of 15, mixed chimeras: 15 of 23, immunodeficient recipients: 16 of 31). In contrast, isotransplants were virtually free of CAV. Three of the four transplanted swine hearts showed neointimal proliferation characteristic of CAV in 1%-6% of donor coronary arteries. Control hearts transplanted into untreated recipients across similar minor antigen barriers were acutely rejected within 44 days whereas control isografts survived indefinitely without evidence of CAV. Conclusions: Elimination of T and B cell immune responses was not sufficient to prevent the development of CAV. Other immune effectors, perhaps NK cells, could play a role in the development of CAV in this immunodeficient state. Additional results on these alternate effectors will be presented.