Conversion of immunogenicity of blood to tolerogenicity by prior platelet transfusions in rabbits

Abstract

Pretransplant blood transfusions have been found to be effective in prolonging renal allograft survival in both experimental animals 12 and humans 3'4. However, the effect of blood transfusions has not been always salutary, but rather reminiscent of a double-edged sword. That is, it often sensitizes the recipients against the histocompatibility antigens of specific donors, 5-7 and a deleterious effect of the presensitization on allograft survival has been well documented, particularly in human renal transplantation. 89 This led to a search for nonimmunogenic yet tolerogenic modalities of transfusion. The techniques reported to be effective include heat treatment of lymphoid cells, ultraviolet irradiation of whole blood, storage of blood, preparation of leucocyte-depleted erythrocytes or platelets, and administration of immunosuppressive drugs along with blood transfusions. Among these techniques, the preparation of leucocyte-depleted platelets seems to be least manipulatory, and moreover could be readily applicable to humans. The earliest observation on platelet-induced tolerance was made in a rat transfusion model, in which purified platelet preparations not only failed to induce antibody production in recipient animals but also suppressed antibody response to subsequent challenge with lymphoid cells, t° The authors attributed such effects to the expression of class I histocompatibility antigens on platelets without class II antigens. This type of humoral immune tolerance has been reported with all other animal models so far tested including mice 11'12 and rhesus monkeys) TM However, in terms of graft tolerance, the effect of platelet pretreatment has not been uniformly salutary. While this treatment was found to be effective in prolonging graft survival in mice, t2 rats ~5 and rhesus monkeys, TM the effect was controversial in dogs t6A7 and humans) s.19 Putting the above findings together, the immunological