Author:
Xie Si,Yang Liu,Bi Xiaoyue,Deng Wen,Jiang Tingting,Lin Yanjie,Wang Shiyu,Zhang Lu,Liu Ruyu,Chang Min,Wu Shuling,Gao Yuanjiao,Hao Hongxiao,Shen Ge,Xu Mengjiao,Chen Xiaoxue,Hu Leiping,Lu Yao,Song Rui,Xie Yao,Li Minghui
Abstract
ObjectiveWe explore the expression of functional molecules on CD8+ T lymphocytes, cytokines concentration, and their correlation to occurrence of hepatitis B and hepatitis B virus (HBV) desoxyribose nucleic acid (DNA), hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), and alanine aminotransferase (ALT) in patients infected with HBV.MethodsThis is a single center study. 32 patients with acute hepatitis B (AHB), 30 patients with immune tolerant (IT) phase chronic HBV infected, and 50 patients with chronic hepatitis B (CHB) were enrolled. The activation molecules (CD69) and the apoptosis-inducing molecules (CD178) on surface of CD8+ T lymphocytes were tested by the flow cytometry. Fms-like tyrosine kinase 3 ligand (Flt-3L), interleukin 17A (IL-17A), interferon γ (IFN-γ), and Interferon α2 (IFN-α2) were quantitated by Luminex assay. We use linear regression analysis to analyze their correlations to ALT, HBV DNA, HBsAg, and HBeAg.ResultsThe frequency of CD69+CD8+ T lymphocytes in CHB and AHB groups were increased significantly compared with IT group (4.19[3.01, 6.18]% and 4.45[2.93, 6.71]% vs. 3.02[2.17, 3.44]%; H=26.207, P=0.001; H=28.585, P=0.002), and the mean fluorescence intensity (MFI) of CD69 in AHB group was significantly higher than IT and CHB groups (27.35[24.88, 32.25] vs. 20.45[19.05, 27.75] and 23.40[16.78, 28.13]; H=25.832, P=0.005 and H=22.056, P=0.008). In IT group, HBsAg levels and HBV DNA loads were negatively correlated with CD69MFI (β=-0.025, t=-2.613, P=0.014; β=-0.021, t=-2.286, P=0.030), meanwhile, HBeAg was negatively related to the frequency of CD69+CD8+ T lymphocytes (β=-61.306, t=-2.116, P=0.043). In AHB group, IFN-α2 was positively related to the frequency of CD8+ T lymphocytes (β=6.798, t=2.629, P=0.016); however, in CHB group, IFN-α2 was negatively associated with frequency of CD8+ T lymphocytes (β=-14.534, t=-2.085, P=0.043). In CHB group, HBeAg was positively associated with frequency of CD69+CD8+ T lymphocytes (β=43.912, t=2.027, P=0.048). In AHB group, ALT was positively related to CD69MFI (β=35.042, t=2.896, P=0.007), but HBsAg was negatively related to CD178MFI (β=-0.137, t=-3.273, P=0.003).ConclusionsThe activation of CD8+ T lymphocytes was associated with the occurrence of AHB and CHB. However, due to the insufficient expression of functional molecules of CD8+ T lymphocytes and the depletion of CD8+ T lymphocytes, CHB patients were difficult to recover from HBV infection.
Funder
Digestive Medical Coordinated Development Center of Beijing Hospitals Authority
National Major Science and Technology Projects of China
Subject
Immunology,Immunology and Allergy