Glucocorticoid Amplifies IL-2-induced Expansion Of CD4~+CD25~+FOXP3~+ Regulatory T Cells In Vivo Selectively And Suppress Graft Verses Host Disease After Allogeneic Lymphocyte Transplantation

Background:Regulatory T cells(Treg) are a subpopulation of T cell that not only prevent autoimmunity but also control a broad range of T-cell-dependent immune responses in vivo.Treg cells inhibit the rejection of transplants,prevent the induction of antitumor responses and regulate the immune response to infectious disease.Glucocorticoid(Dexamethasone,DXM) has been reported to amplify IL-2-mediated selective expansion of Treg cells in vivo.We gave simultaneous administration of DXM and IL-2 to the donor,to markedly expand functional suppressive CD4~+CD25~+FOXP3~+ T cells in the graft,and rise the Treg/Teff ratio to effect the graft-versus-host-diease(GVHD) after allogeneic lymphocyte transplantation.Methods:After combined treatment to donor with DXM(5 mg/kg/day) and IL-2(300,000 IU/mouse/day) for three days,grafts were made Flow cytometry analysis and progress the allogeneic lymphocyte transplantation from male C57BL/6N mice to female BALB/c mice aged 8-12 weeks.Target organ GVHD pathology and host survival were investigated after transplantation.Detections of donor-derived hematopoiesis in mice reconstituted by Y-chromosome-specific PCR and H-2K~b by Flow cytometry were also in progress.Results:Shot-term simultaneous administration of DXM and IL-2 markedly expanded functional suppressive CD4~+CD25~+FOXP3~+ T cells in murine spleen.In a murine allogeneic transplantation model,the grafts from donor with DXM and IL-2 pre-treatment led to longer survival time than the control group(median survival time＞60d vs 12d,P=0.0002).The ratio of regulatory T cells to effector T cells(Treg/Teff) were also increased remarkably(0.43±0.15 vs 0.14±0.01, P=0.01).Conclusions:Costimulation with DXM and IL-2 would selectively expand the functional CD4~+CD25~+FOXP3~+ T cells in vivo,and graft from donor pretreated with DXM and IL-2 led to longer survival time and suppression effect to graft-versus-host disease after the allogeneic transplantation.Thus,the GVHD suppression might due to the expansion of graft regulatory T cells specifically by DXM and IL-2 in vivo.