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Objective:To investigate the changes of non-specific and HBV core antigen (HBcAg)-specific Th9 cells, and intereleukin-9 (IL-9) in HBV-infected patients, and to assess the influence of Th9 cells on CD8 + T cell function. Methods:Twelve patients with acute hepatitis B (AHB) and 58 with chronic hepatitis B (CHB), who were hospitalized in the First Affiliated Hospital of Xinxiang Medical University between January 2018 and January 2019, were enrolled in this study. Twenty healthy subjects negative for HBsAg were selected as controls. Peripheral blood mononuclear cells (PBMCs) and plasma samples were isolated. Non-specific Th9 cells (CD3 + CD4 + IL-9 + ) and HBcAg-specific Th9 cells were analyzed by flow cytometry. Plasma IL-9 level was measured by enzyme linked immunosorbent assay. CHB patients received tenofovir disoproxil fumarate (TDF) antiviral therapy. The changes of non-specific Th9 cells, HBcAg-specific Th9 cells and plasma IL-9 level were assessed 48 weeks after TDF therapy. CD4 + CCR4 -CCR6 -CXCR3 -(Th9) cells and CD8 + T cells were isolated from 12 HLA-A2 restricted CHB patients and co-cultured with HepG2.2.15 cells with the presence of anti-IL-9 neutralizing antibody. The percentage of dead HepG2.2.15 cells and the levels of IFN-γ and TNF-α were detected. Student′s t test, one-way analysis of variance or SNK- q test was used for statistical comparison between groups. Results:There were no significant differences in non-specific Th9 cells or plasma IL-9 level among AHB patients, CHB patients and healthy controls ( P>0.05). HBcAg-specific Th9 cells was down-regulated in CHB patients when compared with AHB patients [(2.49±0.61)% vs (3.19±0.62)%, P<0.001]. The percentage of HBcAg-specific Th9 cells was negatively correlated with HBV DNA ( r=-0.385, P=0.003), but not correlated with ALT ( P>0.05) in CHB patients. TDF therapy for 48 weeks remarkably elevated the HBcAg-specific Th9 cells [(2.94±0.48)%, P<0.001], however, did not affect non-specific Th9 cells or plasma IL-9 level ( P>0.05) in CHB patients. The cytotoxicity of HBcAg-specific Th9 cells was low in CHB patients. However, HBcAg-specific Th9 cells could induce enhanced cytotoxicity of CD8 + T cells to HepG2.2.15 cells, which manifested as increased percentage of dead HepG2.2.15 cells and higher levels of IFN-γ and TNF-α. Anti-IL-9 neutralizing antibody reduced the enhancement of CD8 + T cell cytotoxicity by HBcAg-specific Th9 cells ( P<0.001). Conclusions:Chronic HBV infection might suppress the level and function of HBcAg-specific Th9 cells, resulting in persistent infection.
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OBJECTIVE:To study the influence of compound glycyrrhizin on hepatic fibrosis indices and cytokines in patients with chronic hepatitis B(CHB).METHODS:84 patients with CHB were randomly divided into the treatment group(conventional liver protection+compound glycyrrhizin tablet) and control group(conventional liver protection).The serum levels of transforming growth factor-?1(TGF-?1),tumor necrosis factor-?(TNF-?),hyaluronic acid(HA),collagen type Ⅳ(C-Ⅳ) and laminin(LN) in those patients were measured by specific-ELISA and RIA before and after treatment.The serum levels in 20 healthy subjects were used as normal controls.RESULTS:The serum levels of HA,Ⅳ-C,LN,TGF-?1,TNF-? in patients with CHB were significantly higher than those in healthy subjects(P
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OBJECTIVE:To study the influence of reduced glutathione(GSH) on serum liver fibrosis index and cytokines in patients with chronic hepatitis B(CHB) . METHODS:96 patients with CHB were randomly divided into the treatment group(treated with GSH) and control group. The serum levels of TGF-?1,TNF-?,hyaline acid(HA) ,type Ⅳcollagen(C-Ⅳ) ,laminin(LN) ,Alanine aminotransferase(ALT) and Aspartate Aminotransferase(AST) were measured by specific-ELISA and RIA assay before and after treatment. Healthy group made up of 30 healthy volunteers. RESULTS:Before treatment the serum levels of ALT,AST,TGF-?1,TNF-?,HA,C-Ⅳ and LN in CHB group were significantly increased,as compared with heatthy group(P