Induction of tolerance to vascularised skin allografts using cyclosporin A--an experimental study on rats

This study investigates the induction of tolerance to vascularised skin allografts in a low responder rodent strain combination. Pedicle skin grafts based on the epigastric vessels were grafted between Dark Agouti (DA) and Piebald Virol Glaxo (PVG) rats (n = 24). An extended treatment protocol of high dose cyclosporin A (CyA) (25 mg/kg) spanning nine weeks was used. The mean survival time of epigastric skin grafts in the no treatment control group was 7.6 days (n = 10). With high dose CyA (25 mg/kg), 5/14 animals died during CyA treatment with intact skin grafts. The remaining nine animals enjoyed prolonged graft survival throughout the treatment period. Between one and four weeks following cessation of CyA, rejection occurred in six of nine animals which could not be reversed by pulse CyA treatment. Long term graft survival greater than 200 days was achieved in three animals, but two animals went on to reject their grafts at 231 and 238 days post transplant. Only one animal became tolerant, as confirmed by the retention of a fresh donor-specific free skin graft, without the need for further CyA. This study confirms the difficulty of tolerance induction to vascularised skin grafts, despite using a dose schedule of CyA far in excess of that required to achieve tolerance to other solid organ grafts such as hearts.