The Immune Regulatory Role Of Fetal Bone Marrow-derived Mesenchymal Stem Cells On Human T Lymphocytes

Background and objectives:Although mesenchymal stem cells(MSCs) exert an immune regulatory function,little is known about the interaction between fetal bone marrow-derived MSCs(FBM-MSCs) and immune cells,especially human Th17 cells.The aim of this study was to investigate the immune regulatory role of FBM-MSCs on human T lymphocytes.Materials and methods:In the coculture system,the ratio of FBM-MSCs to the human peripheral blood mononuclear cells(PBMCs) of healthy donors was 1:10.the proliferation assay was measured by MTT.The expression of IL-17,IFN-γ,Foxp3,IL-6,IL-23 was examined by qRT-PCR and the concentration of IL-17 and IFN-γin the supernatants was defected by ELISA.Intracellular cytokine level was performed by flow cytometry.Results:FBM-MSCs suppressed the proliferation of PBMCs induced by PHA and rIL-2 significantly,but increased the percentage of Th Cells.Compared with PBMCs alone group,the higher expression of IL-17 level was detected in MSCs coculture group by qRT-PCR and ELISA analysis.Furthermore,the higher IL-17 was produced by Th17 cells predominantly by flow cytometry analysis.However, FBM-MSCs alone did not express IL-17 protein by using ELISA and flow cytometry analysis.Consistent with enrichment of Th17 cells,higher expression of IL-6 was observed in MSCs coculture group than PBMCs alone group,while no differential expression of IL-23 mRNA was observed between two groups.At the same time,FBM-MSCs upregulated the expression of Foxp3 transcripts.In addition,we found that FBM-MSCs decreased IFN-γproduction in CD4+T cells as well as CD8+T cells. Conclusion:Our data demonstrated for the first time that FBM-MSCs,in vitro, decreased the IFN-γproducing T cells,but contributed to the expansion of Th17 cells and T regulatory cells.The mechanism of Th17 cells expansion was partly through IL-6 instead of IL-23 pathway. Objective:To evaluate the efficacy ofα-interferon(IFN-α) for the treatment of patients with hepatitis-virus related thromboeytopenia.Methods:Twenty patients with hepatitis virus related thrombocytopenia treated with IFN-α.IFN-αwas given at the dose of 3MU subcutaneously twice a week for at least 2 months.Results:Among the 20 patients,14 were males and 6 females,with median age of 36.5 years(7～50).HBV(hepatitis B virus) infection was revealed in 15 patients,HCV(hepatitis C virus) in 4,HBV and HCV co-infection in 1.All the patients presented with thrombocytopenia as the chief complaint and no evidence of cirrhosis,portal hypertension or significant splenomegaly.Complete response(CR) was achieved in 9 patients,partial response(PR) in 6 and minor response(MR) in 2.CR rate was 45%and overall response rate(OR) was 85%.Sustained platelet response was observed.There was no severe side-effect of IFN-α.Conclusion:IFN-αmight be practicable and effective for the treatment of patients with hepatitis virus related thrombocytopenia.