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. In 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 cell lines generated therefrom.


RESULTS
Cop 1 treatment prolonged skin graft survival and inhibited the functional deterioration of thyroid grafts, in various strain combinations, across minor 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-gamma (IFN-gamma) secretion, when incubated in vitro with the stimulating allogeneic cells. Spleen and lymph node cells from Cop 1-treated mice, as well as the T cell lines generated from them, demonstrated a pronounced 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 amounts of Th2 cytokines in response to Cop 1 and small but significant amounts of Th2 cytokines, mainly IL-10, in response to allograft cells.


CONCLUSIONS
Cop 1 treatment inhibited the Th1 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.
Aharoni
R
R
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Teitelbaum
D
D
Arnon
R
R
Sela
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D000068717:Glatiramer Acetate; D006084:Graft Rejection / Q000517:prevention & control*; D006789:Host vs Graft Reaction / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000627:therapeutic use*; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism; D013961:Thyroid Gland / Q000637:transplantation; D014181:Transplantation Immunology
D016207:Cytokines; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate