Genetics of kidney allograft survival in dogs. III. Relevance of histocompatibility matching in immunosuppressed recipients.

Abstract

The relevance of matching for the serologically defined (SD) and lymphocyte-defined (LD) antigens of the major histocompatibility complex (MHC) for renal allograft survival was evaluated in a dog model. Kidney recipients were treated with a standard regimen of immunosuppressive drugs (azathioprine, 2 mg/kg body wt, and prednisolone, 1 mg/kg body wt, daily i.v.) after transplantation. In seven of the eight SD- and LD-identical beagle littermate donor-recipient pairs (DRPs), and in all seven SD- and LD-identical beagle nonlittermate DRPs, kidney function remained normal for the period of 150 days during which immunosuppressants were given. Of the 8 beagle littermate DRPs differing in one haplotype and all 25 unrelated mismatched mongrel DRPs, kidney function deteriorated during immunosuppressive therapy, and most of the recipients died eventually from graft rejection. Thus, it seems that, in moderately immunosuppressive dogs, non-DLA incompatibilities rarely, if ever, cause rejection, whereas DLA incompatibilities almost always do so. The data differ from those obtained in a previous study in nonimmunosuppressed dogs, in which non-DLA incompatibilities seemed to be as strong as DLA incompatibilities in this respect. Differences in minor histocompatibility antigens can apparently be overcome more easily by immunosuppressive drug therapy than differences in major histocompatibility antigens. After the gradual complete withdrawal of immunosuppression, 11 of the 15 matched littermate and nonlittermate DRPs survived for another 150 days or more, implying that some kind of unresponsiveness was induced in those dogs.