Improved renal allograft survival following donor-specific transfusions. III: Kinetics of mixed lymphocyte culture responses before and after transplantation

The essence of the clonal deletion model of the donor-specific transfusion (DST) effect is synergy between DST-priming and post-transplant immunosuppression. Using a sensitive kinetics assay of the mixed lymphocyte culture (MLC) response to donor and third-party stimulators, we compared the responses of controls (non-transfused healthy individuals) with those of patients who either had no rejection episodes in the first week posttransplant (group 1) or who had DST-type (greater than 3d onset) rejection episodes (group 2). We found that group 2 patients had normal or above-normal MLC responses after DST plus azathioprine (AZA) pretransplant treatment, but had a reduced/delayed posttransplant anti-donor MLC following reversal of early rejections (P = .05 compared with controls). Group 1 patients had a nonspecifically reduced MLC after DST + AZA treatment (P less than .02 compared with controls), while posttransplant MLC responses showed a return to normal (pretransfusion) levels. These data suggest a synergy of DST with immunosuppressive drug that induced MLC hyporesponsiveness, but only in patients who received anti-lymphoblast globulin or a sustained high dose immunosuppression in the early posttransplant period.