Contrasting outcomes of donor-specific blood transfusion: Effectiveness against cell-mediated but not antibody-mediated rejection

Background. Giving recipients a prior donor-specific blood transfusion (DST) is effective in prolonging organ allograft survival in some inbred strains but not in others. The present investigation analyzed two such contrasting strains of rats in an attempt to define the basis for this variation. Methods and Results. The survival of fully mismatched Dark Agouti (RT1 a ) cardiac allografts was significantly prolonged (from 7 to 44 days, median survival times) in PVG (RT1 c ) rats given a prior (-14 day) DST, whereas it shortened survival in the high-responder PVG-RT1 u strain. Injecting PVG recipients with blood from strains bearing defined differences indicated that each disparity contributed to the increased survival time in an incremental way: blood and heart matched at the MHC class I (A) and/or class II (B/D) loci had a major influence on survival; class I-like (C) and non-MHC antigens made only minor contributions. MHC disparities had contrasting effects in RT1 u rats. Blood transfusions from Dark Agouti or PVG-R8 (A a B/D u C u ) rats induced accelerated rejection and anti-A a alloantibody formation; transfusing PVG-R23 (A u B/D a C a ) blood, a class II and class I-like difference, induced indefinite R23 heart allograft survival. Although produced in high titer, anti-class II antibody was not able to induce rejection in RT1 u rats. Specific anti-A a alloantibody was able, after passive transfer, to destroy class I-disparate allografts in both RT1 u nude and PVG nude recipients. However, under normal circumstances, acute rejection in the PVG strain occurred in the absence of anti-A a antibodies, presumably by a cell-mediated mechanism. Conclusion. Anti-class I alloantibody, when produced, seemed to override the unresponsiveness induced by DST. The results indicated that DST was effective only when rejection was induced by a cell-mediated response. The two contrasting response patterns in animals may reflect the experience of transplant patients who either benefit from DST or become sensitized instead.