Adoptively transferred donor IL-17-producing CD4^(+) T cells augment, but IL-17 alleviates, acute graft-versus-host disease

摘要

The role of IL-17 and IL-17-producing CD4^(+) T cells in acute graft-versus-host disease(GVHD)has been controversial in recent mouse and human studies.We carried out studies in a murine acute GVHD model of fully major histocompatibility complex-mismatched myeloablative bone marrow transplantation.We showed that donor wild-type CD4^(+) T cells exacerbated acute GVHD compared with IL-17−/−CD4^(+) T cells,while IL-17 reduced the severity of acute GVHD.The augmentation of acute GVHD by transferred donor IL-17-producing CD4^(+) T cells was associated with increased Th1 responses,while IL-17 decreased the percentages of Th1 cells in the GVHD target organs.Furthermore,IL-17 reduced the infiltration of macrophages into the GVHD tissues.In vitro study showed that IL-17 could downregulate Th1 responses,possibly through inhibiting IL-12 production by donor macrophages.Depletion of macrophages in vivo diminished the protective effect of IL-17.Our results demonstrated the differential roles of adoptively transferred donor IL-17-producing CD4^(+) T cells and IL-17 in the same acute GVHD model.