Genetic aspects of the blood transfusion effect.

Abstract

The genetic requirements for the induction of the blood transfusion effect have been investigated in a genetically well-defined model. The survival of fully vascularized, heterotopic murine cardiac allografts was measured after a single preoperative transfusion of blood from mice selected to share MHC and/or minor histocompatibility (miH) antigens with the organ donor. The effect of a transfusion from a donor unrelated to the heart donor (third-party transfusion) on allograft survival was also determined. Five strain combinations were used for these experiments. The results obtained illustrate a number of important aspects of the blood transfusion effect in this model: (1) Donor-specific blood transfusion, where MHC and miH were shared by the blood donor and the organ donor, always induced prolonged graft survival. (2) The sharing of the whole MHC (H-2) by the blood donor and organ donor was found to be sufficient to prolong allograft survival in the five fully allogeneic strain combinations tested. (3) The sharing of miH antigens only was not sufficient to induce prolonged cardiac allograft survival. Special cases were identified showing that several factors could interact to potentiate the action of miH antigens in the induction of the blood transfusion effect. (4) Transfusion with blood from a third-party donor was effective in some strain combinations. In one recipient, blood from several third-party strains of mice, sharing neither MHC nor miH antigens with the organ donor, induced prolonged graft survival. We suggest that the mechanism by which third-party blood has a beneficial effect on graft survival is through crossreaction(s) between the blood donor and the organ donor. The results obtained in this study fit very well with one model for the cellular mechanism by which the transfusion effect may be mediated. This may be the means by which blood from randomly selected donors has a beneficial effect on graft survival in clinical transplantation.