Copolymer 1 inhibits manifestations of graft rejection

Background. Copolymer 1 (Cop 1) was previously shown to prevent graft-versu s-host disease and interfere in various manifestations of immune rejection. I this study, we tested whether Cop 1 can also hinder the reactivity of ho st 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 fu nctional deterioration of thyroid grafts, in various strain combinations, a cross mi nor and major histocompatibility barriers, similarly to the potent immunosuppressive drug FK506. Cop 1 inhibited the proliferation of graft-s pecific T cell lines as well as their interleukin (IL)-2 and interferon(IFN -gamma) secretion, when incubated in vitro with th stimulating allogeneic c ells. 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 p roliferation 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 T h2 cytokines in response to Cop 1 and small bu significant amounts of Th2 c ytokines, mainly IL-10, ii response to allograft cells. Conclusions. Cop 1 treatment inhibited the Th1 re response to graft and ind uced a Th2 cytokines secretion. in response to both Cop 1 and graft cells, leading to improved survival and function of the transplanted grafts.