Cellular mechanisms: Induction of heart allograft survival in rats by 15-deoxyspergualin
Survival of ACI rat heart grafts in Lewis rat (LEW) recipients treated with a short course of 15-deoxyspergualin (DSG), in a dose of 5 mg/kg daily beginning from day 4 of grafting, was markedly prolonged, with a mean survival time of 29.8 ± 3.0 days. On day 20 after grafting, the cellular mechanism of inducing allograft survival after DSG treatment was analyzed by testing the activation of spleen cells in several assay systems. The results indicate that spleen cells from DSG-treated rats with surviving heart allografts show almost no proliferative response against donor strain stimulator cells in the mixed lymphocyte reaction (MLR) as compared with controls. Their cytotoxic activity was lower than that of spleen cells from rats with heart allograft rejection towards donor strain target cells. Adding various concentrations of spleen cells from DSG-treated LEW rats with surviving ACI heart allografts to the MLR when the responder cells frosm normal LEW rats were exposed to irradiated ACI or Wistar (third party) stimulator cells revealed a strong suppression, in a cell-dose-dependent manner. Moreover, the transfer of 2.0 x 108 spleen cells from DSG-treated LEW rats with surviving ACI heart allografts to an irradiated grafted host did not prolong the survival either of the ACI heart grafts or of the third party Wistar heart grafts. These results suggest that the proliferative response and cytotoxic activity are lowered and suppressor cells are induced by treatment with DSG, in rats with surviving allografts.
Key wordsImmunosuppressive agent Heart allograft survival Rejection Spleen cell
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