Copolymer 1 inhibits manifestations of graft rejection

Background. Copolymer 1 (Cop 1) was previously shown to prevent graft-versus-host disease and interfere in various manifestations of immune rejection. I this study, we tested whether Cop 1 can also hinder the reactivity of host against graft and inhibit graft rejection. Methods. Cop 1 was tested in two transplantation systems: skin and thyroid grafting assays. The effect of Cop 1 on T cell reactivity was investigated by proliferation and cytokine secretion of spleen and lymph node cells from transplanted mice, as well as the T cel lines generated therefrom. Results. Cop 1 treatment prolonged skin graft survival and inhibited the functional deterioration of thyroid grafts, in various strain combinations, across mi nor and major histocompatibility barriers, similarly to the potent immunosuppressive drug FK506. Cop 1 inhibited the proliferation of graft-specific T cell lines as well as their interleukin (IL)-2 and interferon(IFN-gamma) secretion, when incubated in vitro with th stimulating allogeneic cells. Spleen and lymph nod cells from Cop 1-treated mice, as well as the T cell line generated from them, demonstrated a pronounced in inhibition of proliferation and secretion of T helper (Th)1 cytokines in response to graft cells. In addition cells from Cop 1-treated mice secreted high amount of Th2 cytokines in response to Cop 1 and small bu significant amounts of Th2 cytokines, mainly IL-10, ii response to allograft cells. Conclusions. Cop 1 treatment inhibited the Th1 re response to graft and induced a Th2 cytokines secretion. in response to both Cop 1 and graft cells, leading to improved survival and function of the transplanted grafts.