title: Myeloid-derived suppressor cells suppress CD4⁺ and CD8⁺ T cell responses in autoimmune hepatitis.
abstract: Myeloid-derived suppressor cells (MDSCs) have been demonstrated with possess the ability to suppress T‑cell responses. Therefore, MDSCs are an attractive candidate for immune intervention aimed at reconstituting self‑tolerance in autoimmune conditions. The present study investigated the frequency and function of MDSCs in the peripheral blood of patients with autoimmune hepatitis (AIH), and examined its correlation with disease progression. Peripheral blood samples were obtained from 48 patients diagnosed with AIH and 24 healthy controls. The frequency of MDSCs was analyzed using flow cytometry, and its correlation with liver biochemical indicators was assessed. The sorted peripheral blood mononuclear cells and MDSCs, cocultivated with CD3 and CD28 monoclonal antibodies, were labeled with carboxylfluorescein succinimidyl ester and detected using flow cytometry for the proliferation of T cells. T cell apoptosis was detected using annexin V and 7‑aminoactinomycin D. Interferon γ and nitric oxide were detected using ELISA, and inducible nitric oxide synthase (iNOS) was detected using immunohistochemical staining. The frequency of MDSCs in the patients with non‑cirrhotic AIH was significantly higher, compared with the healthy controls and patients with cirrhotic AIH (P<0.05). However, no significantly differences were observed between the patients with cirrhotic AIH and the healthy controls (P>0.05). In addition, the frequency of MDSCs in the peripheral blood was positively correlated with alanine transaminase and aspartate transaminase in patients with AIH. The T cells of the incubation system were suppressed by the MDSCs, which was associated with the iNOS expressed on MDSCs. In patients with non‑cirrhotic AIH, the peripheral frequency of MDSCs was increased through a feedback loop and autoimmune responses were inhibited. However, a variety of causes led to a decrease in the number of MDSCs in patients with cirrhotic AIH, therefore, accelerating the progression of liver injury and liver cirrhosis.
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China.
authors.forename: Haiwen
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China.
authors.forename: Fu
authors.initials: F
authors.lastname: Dai
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China.
authors.forename: Huizhong
authors.initials: H
authors.lastname: Gan
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China.
authors.forename: Jishun
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China.
authors.forename: Yunling
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China.
authors.forename: Wanyuan
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000328:Adult; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002469:Cell Separation; D005260:Female; D019693:Hepatitis, Autoimmune / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000276:immunology; D017634:Self Tolerance
chemical_list: C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II