Induction of tolerance to composite tissue allograft in a rat model.
The goal of this study was to establish a rat model that can be used to determine the variables in influencing induction of tolerance to composite tissue allografts. An anti T-cell depleting agent (R73) and 15-deoxyspergualin were given in different doses and schedule to four groups of Lewis rats receiving a limb transplant from Brown-Norway donors. Graft survival prolongation was maximal combining a single dose of R73 and a 20-day administration of 15-deoxyspergualin. Long-term survivors accepted a skin graft from Brown-Norway donors at 80 days, but rejected grafts from an unrelated donor. Skin grafting did not influence survival of the transplanted limb. Mixed allogeneic chimerism was not detectable in peripheral blood by flow cytometry, but immunohistochemistry identified donor-derived cells in the thymus of tolerant recipients at 100 days. These results suggest a state of donor-specific, dynamic tolerance, with potential for future application in human composite tissue allotransplantation.