The pathogenesis of xenograft rejection

The transplantation of vascularized organs between species stimulates an intense rejection reaction by the recipient of the graft. The classification of the xenograft rejection reaction on the basis of the degree of genetic disparity between donor and recipient species and the presence or absence of preformed antibody to the donor tissue does not provide for a precise classification schema. We have proposed that xenograft reactions be classified on the basis of the immunological mechanisms responsible for the loss of the graft. The rejection of xenografts would then be divided into those that are antibody-dependent and mediated by antidonor antibody, either preformed (i.e. pig-to-human xenografts) and present at the time of transplantation or antibody produced in response to placement of the graft (hamster-to-rat). A second group of xenograft reactions would consist of those for which the direct activation of the alternative complement pathway results in loss of the graft in the absence of the binding of antidonor antibody from the recipient (guinea pig-to-rat). The focus on the pathogenesis of xenograft reactions for classification purposes is a more consistent method of description and is more clearly related to future attempts to prevent rejection with immunosuppressive therapy.