THE SURVIVAL AND NATURE OF THE IMMUNE RESPONSE TO SOFT-TISSUE AND COMPOSITE-TISSUE ALLOGRAFTS IN RATS TREATED WITH LOW-DOSE CYCLOSPORINE

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Abstract
We studied a variety of soft-tissue and composite-tissue allografts (CTA) in a histoincompatible rat model to determine the outcome and the nature of the immunologic responses to these tissues using continuous low-dose cyclosporine (CsA) therapy. Brown-Norway (RT1n) rats served as donors of soft tissue and CTA to Lewis (RT11) rat recipients given low-dose CsA immunosup-pressive therapy by gavnge. Nine groups were studied. Three control groups were not treated with CsA: group 1, skin grafts alone; group 2, skin flaps alone; and group 3, skin grafts and delayed vessel allotransplants. Six groups were treated with CsA: group 4, skin grafts alone; group 5, skin flaps alone; group 6, skin grafts and delayed vessel allotransplants; group 7, aortas alone: group 8, muscle flaps alone: and group 9 bone grafts alone. Isografts were performed in all groups as technical controls. The appearance posttransplant of donor-directed cytotoxic antibodies was determined in recipient serum using a complement-mediated cytotoxicity assay and was compared to control and pretransplant sera. In the absence of CsA therapy, recipients in groups 1, 2, and 3 rejected their allografts early (8.5–9.4 days) and developed profound antidonor cytotoxic antibody aetivity posttransplant by day 7. Groups 4, 5, 6, 7, and 9 had prolonged graft survival in the presence of low-dose CsA, despite the presence of antidonor antibody activity. By contrast, group 8 (muscle flaps) were all uniformly rejected in the presence of profound recipient cytotoxic antidonor antibody activity. These results suggest that long-term soft-tissue and CTA survival can be achieved in histoincompatible rat recipients using continuous low-dose CsA immunosuppressive therapy despite the presence of cytotoxic antidonor antibodies.