Association of donor-specific blood transfusion enhancement of rat renal allografts with accelerated development of antiidiotypic antibodies and reduced alloantibody responses

Abstract

Pretransplant donor-specific blood transfusion (DSBT) has been shown to enhance renal allograft survival in man and indefinitely prolong renal transplants among various MHC-disparate rat strains. Using PVG (RT1c) recipients and ACI (RT1a) donor-strain rats, DSBT alone was found to elicit complement-dependent cytotoxic IgM antibody (Ab) to donor class I (RT1.Aa) alloantigens that peaked at 7 days. An enzyme-linked immunosorbent assay was developed to measure host Ab against allospecific (idiotypic) determinants on the anti-RT1.Aa monoclonal Ab R2/10P, R2/15S, and YR1/100. Following DSBT alone, antiidiotypic Ab were detected in the circulation within 7-11 days after transfusion. Transplantation of a donor strain kidney in the presence of antiidiotypic Ab at day 7 or 11 post-DSBT resulted in enhanced graft survival and a rapid decline in circulating alloantibody, such that by days 4-6 posttransplantation little IgM or IgG alloantibody was detected. In contrast, all 6 PVG rats that were transplanted 4 days after DSBT (prior to development of detectable antiidiotypic Ab) rejected their grafts within 30 days, and 4 of 6 showed elevated alloantibody titers within 3 days posttransplantation. Control PVG rats receiving autologous blood transfusion (ABT) alone developed no alloantibody response but developed high titers of donor-specific alloantibody by 6 days posttransplantation, at the time of irreversible rejection. ABT alone did not elicit antiidiotypic Ab and ABT pretreated graft recipients developed antiidiotypic Ab only after the onset of rejection at day 4. In both DSBT and ABT groups, the antiidiotypic Ab were primarily IgM, IgG1, and IgG2c. These findings indicate that DSBT induces production of cytotoxic alloantibodies followed by an antiidiotypic Ab response at days 7-11, during which time transplanted renal allografts are not rejected and there is a reduction in circulating alloantibody. In contrast, renal allografts placed in DSBT-treated rats prior to antiidiotypic Ab development (less than or equal to 4 days) or in ABT-treated rats that do not develop any antiidiotypic Ab, elicit a rapid rise in alloantibody and are rejected.