INFLUENCE OF BLOOD TRANSFUSIONS AND MATCHING FOR DR ANTIGENS ON KIDNEY ALLOGRAFT SURVIVAL IN UNRELATED RHESUS MONKEYS

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Abstract

Summary

Kidney transplantations were performed in unrelated, immunosuppressed rhesus monkeys matched for two DR antigens and given five pretransplant transfusions of whole blood. The host-donor combinations were either reactive or nonreactive in mixed lymphocyte culture (MLC) and shared up to three A and B locus antigens with their blood and kidney donors. Although previous monkey experiments had shown a definite positive influence of DR matching as well as of pretransplant transfusions on graft survival, this was not found in the current experiments (the mean survival time for the MLC responsive group was 21.3 days, for the MLC nonresponsive group 28.2 days). It appears therefore that the combination of pretransplant transfusions and matching for DR antigens does not have an additive or synergistic effect on graft survival. In fact, the prominent transfusion effect demonstrated previously may have been somehow compromised by matching for DR antigens. Alternatively, the clearly positive effect of matching for two DR antigens may have been reduced or lost as a consequence of giving the blood transfusions.

Two recent developments have had a major impact on clinical and experimental transplantation immunology. The first is that it has been shown that multiple blood transfusions given before transplantation can substantially prolong kidney allograft survival (reviewed in Ref. 1). The second is that protection of allografts may be achieved by matching host-donor combinations for the products of the D locus and the closely associated or identical DR locus (reviewed in Ref. 2). Both approaches to the prolongation of kidney allografts have been investigated prospectively in rhesus monkeys. First, it was shown that the administration of blood transfusions before transplantation leads to a considerable improvement of graft prognosis (3, 4). It was subsequently demonstrated that matching unrelated monkeys for DR antigens leads to a significant prolongation of kidney graft survival, at least if recipient lymphocytes are MLC negative against kidney donor cells (5). In view of those results, it was clearly of interest to investigate whether matching for DR antigens combined with pretransplant transfusions would show an additive or even synergistic effect on graft survival.

In the current experiments, kidney transplantations were performed between unrelated immunosuppressed rhesus monkeys that shared two DR antigens but were also given five blood transfusions before transplantation. The host-donor combinations were either reactive or nonreactive in MLC and shared up to three A and B locus antigens with their blood donors as well as their kidney donors. The results were difficult to interpret because, in comparison with controls, no significantly prolonged mean survival times were obtained in the MLR-positive or in the MLR-negative combinations. A number of mechanisms are postulated to explain these unexpected results; they are discussed in the light of the clearly favorable results published previously for recipients which were either matched with their donors for DR antigens (5) or unmatched for DR but given pretransplant transfusions (4).

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