RENAL TRANSPLANTATION IN INBRED RAT .X. A MODEL OF WEAK HISTOINCOMPATIBILITY BY MAJOR LOCUS MATCHING

Using two inbred strains of rats, (Lewis X Fischer) F1 hybrid as donors and Lewis as recipients, we have performed 82 renal allotransplants to study the functional and morphological characteristics of renal allograft rejection in this experimental model. The prolonged survival of renal allografts in nonsensitized recipients is in marked contrast to the prompt rejection of skin grafts in the same donorrecipient combination. The early variability of renal function in nonsensitized recipients usually stabilizes within the normal range; in recipients presensitized with donor strain skin grafts, effective renal plasma flow reveals uniform deterioration, reaching anephric levels by day 7. The accumulation and proliferation of mononuclear cells within the interstitium of the renal allografts in nonsensitized recipients is a reversible phenomenon and not necessarily permanently injurious to the graft. In presensitized recipients, the marked interstitial infiltrate, platelet aggregates in glomerular capillaries, and associated fibrin result in irreversible renal failure. In long-term renal allografts, the interstitial fibrosis, glomerulopathy, and perivascular infiltrate are in keeping with a form of chronic immunological injury to the transplant. The results suggest that this is a satisfactory model to study the natural history of chronic renal allograft rejection in a genetically defined donor-recipient strain combination. Since 3 of 4 of the long-term survivors accept skin grafts from the strain of the kidney donor, and enhancing antibody activity is not demonstrated in their serum, it is concluded that the induction of immunological tolerance is associated with the transient and reversible rejection of these renal allografts across a “weak” genetic barrier. © 1969 by the Williams and Wilkins Co.