ANTILYMPHOCYTE SERUM AND CYCLOPHOSPHAMIDE IN THE INDUCTION OF TOLERANCE TO SKIN ALLOGRAFTS IN GUINEA PIGS

Abstract

Prolonged skin allograft survival was obtained in guinea pigs treated with a combination of antilymphocyte serum (ALS) and cyclophosphamide (CY). Twenty percent of treated animals retained their grafts indefinitely, the majority being followed for over 100 days. Histological examination of the draining lymph nodes indicated that the effect of CY was to suppress those cells involved in humoral antibody production, in addition to the cells involved in cell-mediated immunity which were depleted by ALS. This finding was confirmed by the observation that CY caused a substantial reduction in the level of antibodies against rabbit serum proteins that developed in the sera of guinea pigs treated with ALS alone. It was concluded, therefore, that the action of CY was related to a reduction in the rate of elimination of ALS by circulating antibody. An added feature of these experiments is that they describe prolongation of graft survival after a short course of immunosuppressive therapy, without the associated systemic injection of antigen.