Division of Hepatology, Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Front Immunol. 2022 Oct 24;13:1036612. doi: 10.3389/fimmu.2022.1036612. eCollection 2022.
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.
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.
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]%; =26.207, =0.001; =28.585, =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]; =25.832, =0.005 and =22.056, =0.008). In IT group, HBsAg levels and HBV DNA loads were negatively correlated with CD69MFI (=-0.025, =-2.613, =0.014; =-0.021, =-2.286, =0.030), meanwhile, HBeAg was negatively related to the frequency of CD69+CD8+ T lymphocytes (=-61.306, =-2.116, =0.043). In AHB group, IFN-α2 was positively related to the frequency of CD8+ T lymphocytes (=6.798, =2.629, =0.016); however, in CHB group, IFN-α2 was negatively associated with frequency of CD8+ T lymphocytes (=-14.534, =-2.085, =0.043). In CHB group, HBeAg was positively associated with frequency of CD69+CD8+ T lymphocytes (=43.912, =2.027, =0.048). In AHB group, ALT was positively related to CD69MFI (=35.042, =2.896, =0.007), but HBsAg was negatively related to CD178MFI (=-0.137, =-3.273, =0.003).
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.
探讨乙型肝炎病毒（HBV）感染者 CD8+T 淋巴细胞功能分子的表达、细胞因子浓度及其与乙型肝炎和 HBV 脱氧核糖核酸（DNA）、乙型肝炎表面抗原（HBsAg）、乙型肝炎 e 抗原（HBeAg）、丙氨酸氨基转移酶（ALT）发生的相关性。
这是一项单中心研究。纳入 32 例急性乙型肝炎（AHB）患者、30 例免疫耐受期慢性 HBV 感染患者和 50 例慢性乙型肝炎（CHB）患者。采用流式细胞术检测 CD8+T 淋巴细胞表面的激活分子（CD69）和凋亡诱导分子（CD178）。采用 Luminex assay 定量检测 Fms 样酪氨酸激酶 3 配体（Flt-3L）、白细胞介素 17A（IL-17A）、干扰素γ（IFN-γ）和干扰素α2（IFN-α2）。采用线性回归分析来分析它们与 ALT、HBV DNA、HBsAg 和 HBeAg 的相关性。
CHB 组和 AHB 组 CD69+CD8+T 淋巴细胞的频率明显高于 IT 组（4.19[3.01, 6.18]%和 4.45[2.93, 6.71]%与 3.02[2.17, 3.44]%；=26.207，=0.001；=28.585，=0.002），且 AHB 组 CD69 的平均荧光强度（MFI）明显高于 IT 组和 CHB 组（27.35[24.88, 32.25]与 20.45[19.05, 27.75]和 23.40[16.78, 28.13]；=25.832，=0.005；=22.056，=0.008）。在 IT 组中，HBsAg 水平和 HBV DNA 载量与 CD69MFI 呈负相关（=-0.025，=-2.613，=0.014；=-0.021，=-2.286，=0.030），同时，HBeAg 与 CD69+CD8+T 淋巴细胞的频率呈负相关（=-61.306，=-2.116，=0.043）。在 AHB 组中，IFN-α2 与 CD8+T 淋巴细胞的频率呈正相关（=6.798，=2.629，=0.016）；然而，在 CHB 组中，IFN-α2 与 CD8+T 淋巴细胞的频率呈负相关（=-14.534，=-2.085，=0.043）。在 CHB 组中，HBeAg 与 CD69+CD8+T 淋巴细胞的频率呈正相关（=43.912，=2.027，=0.048）。在 AHB 组中，ALT 与 CD69MFI 呈正相关（=35.042，=2.896，=0.007），但 HBsAg 与 CD178MFI 呈负相关（=-0.137，=-3.273，=0.003）。
CD8+T 淋巴细胞的激活与 AHB 和 CHB 的发生有关。然而，由于 CD8+T 淋巴细胞功能分子表达不足和 CD8+T 淋巴细胞耗竭，CHB 患者难以从 HBV 感染中恢复。
