Frequency And Function Study Of Myeloid Derived Suppressor Cells In Autoimmune Hepatitis Patients

Background Autoimmune hepatitis (AIH) is a kind of chronic and autoimmune inflammation of the liver, which is characterized by interface hepatitis in histology, hypergammaglobulinemia, and production of autoantibodies. As involved in the mechanisms of AIH, the self-tolerance, normally keeping the response to self-antigens under control, also named homeostatic processes in autoimmune disease, is defect. The derangement of immune homeostatic leads to T-lymphocytes immune responses out of control, such as over activated CD4 and CD8 T-cells, both involved in the autoimmune liver attack. Evidence provided recently has indicated that regulatory cells such as regulatory T-cells and NK T cells are key to the maintenance of immune tolerance in AIH. One population of the regulatory cells which de?ned Myeloid-Derived Suppressor Cells (MDSCs) has been regarded closely for their remarkable ability to suppress T-cell responses, thus they represent an attractive candidate for immune intervention aiming at reconstituting self-tolerance in autoimmune conditions.Objective To investigate the frequency and function of myeloid-derived suppressor cells in peripheral blood in patients with autoimmune hepatitis and its correlation with disease progression.Methods Peripheral blood samples from 48 AIH patients and 24 healthy controls were collected. The frequency of MDSCs was analyzed using flow cytometry and its correlation with liver biochemical indicators was evaluated as well. Sorted PBMC and MDSCs cocultivated with CD3 and CD28 monoclonal antibody, then lebaled CFSE and detected by FCM for proliferation of T cells. Apoptosis of T cells was detected by annexin V and 7AAD. INF–and NO of incubation system was detected by ELISA, and iNOS of liver tissue was detected by immunohistochemical.Results The frequency of MDSCs in non-cirrhotic AIH patients was significantly higher than healthy controls and cirrhotic AIH patients (P<0.05), but there were no significantly differences between cirrhotic AIH patients and healthy controls (P>0.05).Moreover, the frequency of MDSCs in peripheral blood was positively correlated with ALT and AST in AIH patients.T cells of incubation system was suppressed by MDSCs, which associated with iNOS that expressed on MDSCs.Conclusion In non-cirrhotic AIH patients, the peripheral frequency of MDSCs was enhanced through feedback loop and autoimmune responses were inhibited. However, a variety of causes lead to the decrease in the number of MDSCs in cirrhotic AIH patients, thus accelerating the progress of liver injury and liver cirrhosis.