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Modification of immunogenicity of transfusion products
Abstract:
The transfusion of foreign blood products (expressing non-self histocompatibility antigens) leads to an immune response in the transfusion recipient. This may result in a memory response to subsequent transfusions, and in patients undergoing marrow transplantation for the treatment of aplastic anemia in an increased risk of marrow graft rejection. We have used the canine model of marrow transplantation as an in vivo indicator system for the occurrence of post transfusion sensitization. Our results show that sensitization can occur in response not only to major histocompatibility complex (DLA) antigens but also to minor (non-DLA) antigens. Our studies suggest that the antigens involved are probably expressed on leukocytes but not on RBC and platelets. Among leukocytes the sensitizing population appears to be contained within mononuclear cells, presumably large Ia positive cells which show accessory cell function in vitro. The responsible antigens are apparently not expressed on T lymphocytes. Our findings are in agreement with the hypothesis that dendritic cells play a central role in transfusion-induced sensitization. Their sensitizing ability can be abrogated by exposure to UV light prior to transfusion. It is conceivable that exposure to UV light alters the function of Ia antigens which in turn results in defective antigen presentation and consequently a lack of sensitization of the recipient. Alternatively non-DLA antigens on donor cells could be modified by exposure to UV light thus escaping recognition by the recipient. The exact mechanism remains to be determined.