Studies on the specific suppression of renal allograft rejection in presensitised rats. Theoretical and clinical implications

Abstract

DA and Lewis rats were sensitised by two (DA times Lewis)F1 skin allografts 6 weeks apart and were given a (DA times Lewis)F1 renal allograft 4 weeks after the second skin allograft. Passive enhancement was tbsted in both strain combinations, the (DA times Lewis)F1 to DA model representing the weaker histocompatibility barrier as judged by renal allograft rejection. Passive enhancemnt was much less effective in the sensitised weaker model and was sometimes virtually ineffective in the sensitised stronger model. The powerful combination of antilymphocyte serum and enhancing serum could only delay but not prevent rejection in the latter model. Thus, the avoidance of sensitisation might be of critical importance for the clinical applicability of passive enhancement. Furthermore, it was shown that a sensitised cellular immune system is susceptible to specific immunosuppression, but the result depends on the strain combination used and whether the test graft is skin or kidney. A hypothesis is presented to explain the basis for the difference in strength of different histocompatibility barriers and also the differences between skin and kidney allograft rejection, based on the affinity of surface receptors of lymphocytes for histocompatibility antigens. It was also shown that sensitisation to minor histocompatibility antigens in the Ag-B-compatible AS to Lewis combination led to fierce rejection of a subsequent renal allograft, which was not rejected by the nonsensitised recipient.