The survival of renal allografts between SLA-matched swine has been found to be subject to non-SLA-linked Ir gene control. Using three herds of miniature swine, each homozygous for a different SLA haplotype (designated aa, cc, and dd, respectively), we initially observed that all animals of the c haplotype rejected SLA-matched renal allografts. In contrast, the subset of dd animals which were the product of continuous homozygous matings since establishment of the dd herd (ddR) accepted SLA-matched grafts indefinitely without any immunosuppression. A formal backcross study was therefore performed in which offspring of (cd × ddR) matings (designated cdbc and ddbc) were bilaterally nephrectomized and transplanted with SLA-matched renal allografts. Acceptors and rejectors were found among both backcross types, with a total of 6 of 17 (35%) of the animals dying of renal failure secondary to rejection. When ddbc animals were used as donors for ddR recipients, all grafts were accepted, ruling out the possibility that rejection was attributable to strong non-SLA antigens segregating within the cc herd. These results are consistent with a model in which rejection of SLA-matched renal allografts is controlled by either one or two non-SLA-linked immune response genes. These findings raise the possibility that the observed 5 to 15% frequency of rejection of HLA-identical living related donor renal allografts in man could involve similar immune response gene control.
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