Active enhancement of rat kidney allografts. Effect of pretreatment with prednisolone and donor-specific antigen.

(Lewis x Brown Norway) F1 hybrid rat kidney allografts were transplanted to bilaterally nephrectomized Lewis recipients pretreated in various ways. The mean survival time of untreated controls was 16.1 +/- 1.7 days. All rats pretreated with 1.67 g/kg of semi-soluble Brown Norway spleen extract and 5 mg/kg of prednisolone on days 15, 8, and 1 before transplantation survived indefinitely. Pretreatment with semi-soluble or soluble extract alone prolonged survival modestly (36.5 +/- 13.6 and 30.8 +/- 5.6 days, respectively), but the former induced indefinite survival in two of eight animals. Prednisolone on its own failed to bring about prolongation of survival and the combined use of soluble extract and prednisolone did not reveal a synergistic effect. Cytotoxic antibody titres in animals showing indefinite survival were very low, and there was no correlation between antibody titres and prolonged survival. It is assumed that the pretreatment with semi-soluble extract and prednisolone inhibited the formation of cytotoxic antibodies as well as cell-mediated immunity, and encouraged the formation of enhancing antibodies. To study the cellular and humoral reactivity of five prolonged survived kidney recipients, 1st and 2nd donor-specific skin grafts were carried out. The humoral and cell-mediated responses were somewhat delayed in these recipients but otherwise normal except for the absence of the second-set phenomenon.