Relationship between the effect of cyclophosphamide on adjuvant arthritis severity, skin allograft rejection and spleen cell cytotoxic activity in rats

Cyclophosphamide, which has a poor immunosuppressive effect on adjuvant arthritis in rats, evokes an aggravating form of the disease when applied at a single low dose before rats' sensitization with complete Freund's adjuvant. However, cyclophosphamide administered by this method of treatment has no such enhancement effect on skin allograft rejection reaction; on the contrary, the rejection reaction was inhibited. Spleen cell cytotoxic activity against 51-Cr labelled chondrocytes significantly decreased in adjuvant arthritis, while in skin allograft rejection it increased during the latent period before the rejection reaction appeared. The addition of cyclophosphamide to the rats' treatment decreased more strongly spleen cell cytotoxic activity, especially in rats with adjuvant arthritis. We conclude that cyclophosphamide-sensitive spleen cytotoxic cells are playing a dual role in the pathogenesis of these two cell-mediated immunological processes: as immunosuppressive regulatory cells in adjuvant arthritis and as effector cells in skin allograft rejection reaction.