Composite tissue (limb) allografts in rats. I. Dose-dependent increase in survival with cyclosporine.

The dose-response effect of cyclosporine on rat limb transplant prolongation was investigated across the LBN-to-LEW histocompatibility barrier. This composite tissue allograft model has been shown to represent a strong transplantation barrier. Median limb allograft survival times increased in a dose-dependent manner with low cyclosporine doses, and then reached a plateau at higher levels. The cyclosporine dose that produced half-maximal survival based on a 20-day treatment was only 3.7 mg/kg/day. Histopathology revealed that the rejection process was distinctly different in limb allografts treated with cyclosporine compared with non-cyclosporine-treated controls. Rejection appeared to be delayed or partly arrested in certain areas of cyclosporine-treated limb allografts. These studies represent an initial step in laying the experimental foundation for clinical transplantation of composite tissue allografts using cyclosporine-induced immune suppression.