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.