Shi Xu, Tang Ying, Sun Xiguang, Liu Yufei, Sun Ying, Sun Munan, Jiang Yanfang, Li Yulin
The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130000, P.R. China.
Department of Respiration, The First Hospital, Jilin University, Changchun, Jilin 130032, P.R. China.
Mol Med Rep. 2016 Nov;14(5):4837-4843. doi: 10.3892/mmr.2016.5844. Epub 2016 Oct 13.
The current study aimed to investigate the distribution of memory and naïve T cell (TN) subsets in hepatitis B virus (HBV)‑infected patients at different immune stages and investigate the effect of interleukin 33 (IL‑33) on the regulation of the T‑cell subsets. The distributions of memory and naïve T cells were detected by flow cytometry. ELISA was conducted to assess the levels of IL‑4, IL‑5, IL‑10, IL‑12, interferon γ and tumor necrosis factor α. The expression levels of IL‑33 and HBV x protein (HBx) were measured by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. By detecting TNs, central memory T cells (TCM) and effector memory T cells (TEM), it was identified that the proportions of TCM and TEM in CD4+ T cells were increased in patients with HBV. The trend observed for levels of CD8+ TCM and TEM was similar to that of CD4+ T cells in the immune tolerance and immune activation groups, however CD8+ TCM and TEM were significantly reduced in patients who underwent treatment. The CD8+ TEM cells appeared to be more sensitive to HBV activation and drug therapy. In addition, IL‑33 stimulation was observed to induce imbalances of CD8+ TN and CD8+ TEM, and while the imbalances were directly regulated by HBx, IL‑33 was not a key factor for the expression of HBx. CD8+ TEM cells may be a sensitive marker to assess the immune state of patients with HBV and the effect of clinical therapy. Treatment targeting IL‑33 may be a potential method to reverse HBV‑induced immune tolerance.
本研究旨在调查不同免疫阶段的乙型肝炎病毒（HBV）感染患者中记忆性和初始T细胞（TN）亚群的分布，并研究白细胞介素33（IL-33）对T细胞亚群调节的影响。通过流式细胞术检测记忆性和初始T细胞的分布。采用酶联免疫吸附测定（ELISA）法评估IL-4、IL-5、IL-10、IL-12、干扰素γ和肿瘤坏死因子α的水平。分别通过逆转录定量聚合酶链反应和蛋白质免疫印迹分析检测IL-33和HBV X蛋白（HBx）的表达水平。通过检测TN、中枢记忆T细胞（TCM）和效应记忆T细胞（TEM），发现HBV患者CD4+ T细胞中TCM和TEM的比例增加。在免疫耐受和免疫激活组中，CD8+ TCM和TEM水平的变化趋势与CD4+ T细胞相似，但接受治疗的患者中CD8+ TCM和TEM显著减少。CD8+ TEM细胞似乎对HBV激活和药物治疗更敏感。此外，观察到IL-33刺激可诱导CD8+ TN和CD8+ TEM失衡，虽然这种失衡直接受HBx调节，但IL-33不是HBx表达的关键因素。CD8+ TEM细胞可能是评估HBV患者免疫状态和临床治疗效果的敏感标志物。针对IL-33的治疗可能是逆转HBV诱导的免疫耐受的一种潜在方法。
