Infectious tolerance mediated by CD8 + T-Suppresor Cells After UV-B–irradiated donor-specific transfusion and rat heart transplantation

CD8+CD28− human T-suppressor cells (Ts), which can be generated in vitro, act directly on APC rendering them tolerogenic to unprimed and primed CD4+ T cells. The aim of this study was to investigate the possibility that CD8+ T cells mediate the induction of tolerance in a heart transplantation model in rodents. Blood from Lewis rats was UV-B–irradiated and transfused into ACI recipients on days -21, -14, and -7 before heart allograft transplantation on day 0. CD4 + and CD8 + T cells were positively selected from ACI rats, which had tolerated Lewis heart allografts for more than 100 days and were adoptively transferred to naïve ACI rats pretreated (day -1) with gamma irradiation. These ACI rats underwent transplantation with Lewis hearts 24 hours after adoptive transfer of putative T-suppressor cells. Adoptive transfer of CD8 + T cells from tolerant ACI to naïve ACI rats significantly prolonged Lewis heart mean allograft survival time (MST ± SD) to 69 ± 13 days as compared with 15 ± 1 and 14 ± 1 days in animals adoptively transferred with CD4+ T cells or untreated controls, respectively ( P < .001). Similarly, adoptive transfer of CD8 + T cells from secondary ACI recipients to naïve syngeneic animals also significantly prolonged survival of heart allografts to MST ± SD of 72 ± 4 for CD8 + and 15 ± 4 days for CD4 + T cells ( P < .001). These data demonstrate that allogeneic tolerance induced in ACI recipients by treatment with UV-B–irradiated blood from Lewis donors is mediated by CD8+ T-suppressor cells.