MARKED PROLONGATION OF RAT SKIN XENOGRAFTS INDUCED BY INTRATHYMIC INJECTION OF XENOGENEIC SPLENOCYTES AND A SHORT-COURSE OF RAPAMYCIN IN ANTILYMPHOCYTE SERUM-TREATED MICE

The effect of intrathymic (IT) injection of donor splenocytes and a short course of rapamycin (Rapa) treatment on rat to mouse skin xenograft survival was investigated, ACI rat skin xenografts were transplanted to (C57BL/6xA)F1 mice treated with rabbit anti-mouse lymphocyte serum (ALS) on days -1, +2, and +4 relative to skin grafting on day 0. Fifty million donor-type splenocytes were injected intrathymically on day 7 after transplantation. Rapa was given intraperitoneally every other day from day 0 to day 12 at a dose of 3.0 mg/kg. Prolonged skin xenograft survival was observed in ALS- and Rapa-treated recipients (no IT injection) with a median survival time of 47 days. However, skin graft survival was markedly more prolonged in the group treated with ALS, Papa, and IT injection of donor-type splenocytes with a median survival time of 100 days. Cyclosporine combined with IT injection of donor splenocytes did not have a beneficial effect on skin xenograft survival in ALS-treated recipients. An increased presence of donor-type cells was observed in the thymus of the ALS- and Rapa-treated recipients for 7 days after IT injection of donor splenocytes. In conclusion, a short course of Rapa markedly augments rat skin xenograft survival in ALS-treated mice injected intrathymically with donor-type splenocytes.