Cytokine profiles and CD8+ T cells in the occurrence of acute and chronic hepatitis B.

Objective: We 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.
Methods: This 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.
Results: The 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).
Conclusions: The 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer LJ declared a shared parent affiliation with the authors to the handling editor at the time of review.
(Copyright © 2022 Xie, Yang, Bi, Deng, Jiang, Lin, Wang, Zhang, Liu, Chang, Wu, Gao, Hao, Shen, Xu, Chen, Hu, Lu, Song, Xie and Li.)