A study on the mechanism of donor pretreatment: effect of procarbazine hydrochloride and methylprednisolone in immunocompetent cells.

Significantly prolonged canine renal allograft survival can be obtained by donor pretreatment with procarbazine hydrochloride and methylprednisolone. This is thought to be caused either by a reduced antigenicity of the graft or by a local immunosuppressive effect by drugs transplanted with the graft. In this study a decrease in the number of peripheral donor T and B lymphocytes was observed at the time of procuring. Leukocytes harvested from dogs pretreated with a combination of procarbazine hydrochloride and methylprednisolone showed a decrease in their ability either to stimulate or respond to mixed leukocyte cultures (MLCs). Complete restoration of MLC responses was obtained however by purification and washing of these leukocytes. Sera of pretreated animals were not able to reduce MLC responses. It was concluded that drug metabolites in or on the cells were apparently responsible. A local inhibition of the immunocompetence of host lymphocytes by small amounts of transplanted drug metabolites in or on the graft cells might be responsible for the beneficial effect of donor pretreatment with procarbazine hydrochloride and methylprednisolone. Furthermore, this postulation explains the abrogation of prolonged survival of pretreated grafts after systemic administration of nontreated donor blood or donor leukocyte-free blood, as we reported earlier.