The abrogation of allosensitization following the induction of mixed allogeneic chimerism

The association of preformed anti-donor Abs with the hyperacute rejection o f bone marrow and solid organ allografts and the persistence of the anti-do nor immune response secondary to immunologic memory make allosensitization an absolute contraindication to transplantation. Mixed allogeneic (A + B->A ) bone marrow chimerism has been demonstrated to confer donor-specific tole rance in nonsensitized recipients, but has not been evaluated in the settin g of allosensitization. The current study documents that despite significan t anti-donor sensitization, mixed allogeneic engraftment is possible and pr ovides a marked advantage over fully allogeneic (B->A) models. Moreover, th e acceptance of donor skin grafts and loss of circulating anti-donor Abs su ggest that allosensitization can be abrogated with the induction of stable mixed allogeneic chimerism.