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Effects of Telbivudine Treatment on the Circulating CD4+ T-Cell Subpopulations in Chronic Hepatitis B Patients

机译:替比夫定治疗对慢性乙型肝炎患者循环CD4 + T细胞亚群的影响

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摘要

CD4+ T cells serve as master regulators of the adaptive immune response to HBV. However, CD4+ T-cell subsets are heterogeneous, and it remains unknown how the antiviral agents affect the different CD4+ T cell subtypes. To this end, the expressions of signature transcription factors and cytokines of CD4+ T-cell subtypes were examined in hepatitis B patients before and after treatment with telbivudine. Results showed that, upon the rapid HBV copy decrease induced by telbivudine treatment, the frequencies and related cytokines of Th17 and Treg cells were dramatically decreased, while those for Th2 cells were dramatically increased. No obvious changes were observed in Th1 cell frequencies; although, IFN-γ expression was upregulated in response to telbivudine treatment, suggesting another cell source of IFN-γ in CHB patients. Statistical analyses indicated that Th17 and Tr1 (a Treg subtype) cells were the most sensitive subpopulations of the peripheral blood CD4+ T cells to telbivudine treatment over 52 weeks. Thus, Th17 and Tr1 cells may represent a suitable and effective predictor of responsiveness during telbivudine therapy. These findings not only improve our understanding of hepatitis pathogenesis but also can aid in future development of appropriate therapeutic strategies to control viral hepatitis.
机译:CD4 + T细胞是HBV适应性免疫反应的主要调节因子。然而,CD4 + T细胞亚型是异质的,尚不清楚抗病毒剂如何影响不同的CD4 + T细胞亚型。为此,在替比夫定治疗前后,检测了乙型肝炎患者特征性转录因子的表达和CD4 + T细胞亚型的细胞因子。结果显示,在替比夫定治疗引起的HBV快速复制减少后,Th17和Treg细胞的频率和相关细胞因子显着降低,而Th2细胞的频率和相关细胞因子则显着增加。 Th1细胞频率未见明显变化;尽管,根据替比夫定治疗,IFN-γ的表达上调,提示CHB患者存在另一种IFN-γ的细胞来源。统计分析表明,Th17和Tr1(一种Treg亚型)细胞是替比夫定治疗52周后对外周血CD4 + T细胞最敏感的亚群。因此,Th17和Tr1细胞可能代表替比夫定治疗期间反应的合适和有效预测因子。这些发现不仅增进了我们对肝炎发病机制的了解,而且还有助于控制病毒性肝炎的适当治疗策略的未来发展。

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