INHIBITION OF THE ACCUMULATION, IN RAT KIDNEY ALLOGRAFTS, OF SPECIFIC—BUT NOT NONSPECIFIC—CYTOTOXIC CELLS BY CYCLOSPORINE

Abstract

Rats receiving kidney allografts were divided into 2 groups.sbd.one was treated daily with an immunosuppressive dose of cyclosporine and the other left untreated. Five days after transplantation the cells infiltrating the grafts were extracted by enzymic treatment and tested in vitro for specific and nonspecific cytotoxicity in a 6-h 51Cr release assay. Approximately 5 .times. 107 and 7 .times. 107 mononuclear cells per kidney were obtained, respectively, from healthy grafts excised from cyclosporine-treated hosts and from grafts undergoing unmodified rejection. Despite these similarities in yield the cells harvested from the grafts of the 2 groups showed very different cytolytic activity. Cells from both sources displayed comparable levels of nonspecific cytotoxicity, but only those obtained from grafts undergoing rejection were able to mediate specific target cell lysis. The relevance of these observations to the understanding of the mechanism of kidney allograft rejection in the rat and of the mode of action of cyclosporine are briefly discussed.