PREVENTION OF PLATELET ALLOIMMUNIZATION IN DOGS WITH SYSTEMIC CYCLOSPORINE AND BY UV-IRRADIATION OR CYCLOSPORINE-LOADING OF DONOR PLATELETS

Abstract

To study the immunosuppressive effects of three different treatments, 30 dogs received at weekly intervals eight platelet transfusions from a single random donor dog. The three experimental protocols were (1) daily oral cyclosporine (Cs) treatment of recipients; (2) in vitro ultraviolet (UV)-irradiation of donor platelets; and (3) Cs-loading of donor platelets. All nine recipients of Cs, 11/12 (92%) recipients of UV-irradiated platelets, and 5/9 (56%) recipients of Cs-loaded donor platelets remained nonimmunized to repeated transfusions of donor platelets. In contrast, only 3 of 21 untreated controls (14%) were not alloimmunized by donor platelets. Moreover, 44% to 67% of the nonimmunized recipients remained tolerant to continued platelet transfusions from their original donor even after experimental therapy was discontinued. Forty-three percent to 100% of transfusions from secondary donors were also accepted without causing alloimmunization, suggesting that tolerance induced by prior treatment was not specific for the primary donor. However, survival of both the original and secondary donor platelets was reduced to about half the starting level, suggesting that some immune response to platelets had occurred. Also, recipients immunized by their original donor''s platelet frequently developed refractoriness to platelets from other donors.