INDUCTION OF SPECIFIC TRANSPLANTATION TOLERANCE ACROSS XENOGENEIC BARRIERS IN THE T-INDEPENDENT IMMUNE COMPARTMENT

After transplantation of primarily vascularized xenografts (Xgs), T-in dependent mechanisms may lead to Xg rejection before T-cell activation even takes place. The possibility of achieving T-independent xenotole rance was evaluated in nude rats that normally reject hamster cardiac Xgs within 4 days by non-T cell-mediated mechanisms. After donor antig en infusion, temporary NK-cell depletion and a 4-week administration o f Leflunomide, hamster heart grafts survived even after withdrawal of immunosuppression. Tolerant rats accepted second hamster hearts, but p romptly rejected mouse heart Xgs. In vivo immunization and in vitro cy totoxicity assays indicated that this species-specific tolerance was b ased on B-lymphocyte and NK-cell tolerance respectively.