Enhanced allograft survival by combined active and passive immunization: Requirement of both erythrocytes and leukocytes

(L × BN)F1 skin and heart allografts survive about 7 days in unmodified L hosts. Their survival is only prolonged modestly by active immunization with LBN splenocytes or passive immunization with hyperimmune serum, but the combination of active and passive immunization produces dramatic improvement in graft survival. When the components of this synergistic interaction were analyzed, it was found that not only were lymphocyte-borne antigens and antibodies directed against these antigens important, but also that erythrocyte-borne serologically determined antigens and anti-erythrocyte antibodies were required for optimal survival of both skin and heart allografts. Furthermore, thymic or lymph node cells supplemented with erythrocytes were as effective a source of antigen as whole spleen in prolonging graft survival. These data indicate that, in allograft models in rats, antigens and antibodies that may be of minor importance in producing enhancement when administered individually may be more important when administered together. The underlying basis for the increased effectiveness of erythrocyte-borne antigens and anti-erythrocyte antibodies may be related to the observation that the injected erythrocytes remain in the allogeneic host's circulation to interact with the subsequent i.v. injection of antisera to form soluble antigen-antibody complexes.