| Summary |
The effectiveness of posttransplant total lymphoid irradiation (TLI) given in conjunction with low dose antithymocyte serum (ATS) was determined in the rat skin allograft model. Male Lewis rats (RT-1¹) served as recipients and male Wistar Furth rats (RT-1u) were donors. Full thickness skin allografts were performed and followed for signs of rejection. Preliminary studies revealed the optimal dose and schedule of those tested to be 2.0 Gy every 48 hours beginning on day 1 posttransplant (8.0 Gy total dose). ATS was given on postoperative days -1, 0, and +1. Mean allograft survival time in animals receiving no immunosuppression was 8.5 days. Mean graft survival time was increased from 16.6 days with ATS alone to 23.1 days when TLI and ATS were administered concurrently. No toxicity was noted from either treatment and there was no mortality. White blood cell counts were monitored in all groups for the life of the skin grafts, and circulating lymphocyte counts were monitored in the group of animals that received combination therapy, along with the controls for this group. When the combination of TLI and ATS was used, there was a more drastic decrease in circulating lymphocytes and these values remained low for a more extended period of time. Skin graft tissue samples were stained by immunoperoxidase with the antibodies W3/13 (T cells), W3/25 (helper T cells), 0X8 (cytotoxic/suppressor T cells), and in some cases 0X12 (rat IgG). The data indicated the lymphocytic infiltration in the dermal region of rejecting allografts of rodents receiving ATS and TLI was predominantly of the cytotoxic/suppressor subset. In contrast, in rodents receiving no immunosuppression, ATS only, or TLI only, the predominant cells were of the helper/inducer subset, or both the helper/inducer and cytotoxic/suppressor subsets were present in comparable numbers. Also, there was significant infiltration by cells bearing surface IgG in rodents receiving posttransplant TLI and perioperative ATS. In rodents receiving pretransplant splenectomy with posttransplant TLI and perioperative ATS, cells bearing surface IgG infiltrated at a more rapid pace, and presumably play a more important role in rejection. This indicated the spleen may have been involved in delaying rejection. The splenectomized animals tended to have accelerated rejection times, a phenomenon supported in the literature (Kahn, et al., 1980). |
