Failure of cyclosporine to prevent in vivo T cell priming in man: Studies in allogeneic spleen transplantation

Cyclosporine is a potent new immunosuppressive agent utilized in clinical organ transplantation. Available evidence suggest that it interferes with the secretion of interleukin-2. However, the long term efficacy of cyclopsorine in preventing allograft rejection may depend on a relative sparing of suppressor cells early in the allogeneic response, allowing them to mature and effect a state of operational tolerance. If this is the case, cyclosporine must not affect antigen priming or recognition. Two patients in our center underwent allogensic spleen transplant in conjunction with renal and pancreatic transplant. Both patients were treated with therapeutic levels of cyclosporine during the course of transplant. Neither developed any clinical signs of renal or pancreatic transplant rejection. Both patients developed graft-versue-host disease and eventually required allogeneic (donor) splenectomy. Studies performed on the splenocytes recovered from these specimens demonstrate alloantigen-specific cytotoxic T cell precursors. These studies demonstrate that although cyclosporine can prevent allograft rejection it does not necessarily prevent or ameliorate graft-versus-host disease. Furthermore, cyclosporine does not prevent in vivo T cell priming of alloantigen recognition. The primed cytotoxic precursors can be expanded in the presence of exogenous interleukin-2 to become fully active cytoxic cells.