High frequency of CD4+ CXCR5+ TFH cells in patients with immune-active chronic hepatitis B.
High frequency of CD4+ CXCR5+ TFH cells in patients with immune-active chronic hepatitis B.
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DOI：
10.1371/journal.pone.0021698
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Feng J;Lu L;Hua C;Qin L;Zhao P;Wang J;Wang Y;Li W;Shi X;Jiang Y
滤泡辅助性T细胞（TFH）是一种特殊的辅助性T细胞亚群，可调节体液免疫应答。本研究旨在探讨慢性B型肝炎（CH B）患者中CD 4 + CXCR 5 + TFH细胞的频率是否与主动免疫相关。通过流式细胞术分析表征免疫活性（IA）、免疫耐受（IT）CHB和健康对照（HC）中外周血CD4 + CXCR5 + TFH细胞、诱导性T细胞共刺激分子（ICOS）和/或程序性死亡1（PD-1）阳性CD4 + CXCR5 + TFH细胞的频率。观察adevofir diforxil对IA患者外周血CD4 + CXCR5 + TFH细胞比例、血清IL-2、IFN-γ、TNF-α、IL-4、IL-6、IL-10、IL-21、ALT、AST、HBsAg、HBeAg、HBeAg、HBeAg、HBeAg、HBV载量的影响。分析了CD4 + CXCR5 + TFH细胞频率与临床指标的潜在相关性。此外，还检测了HBV转基因小鼠脾脏和肝脏CD4 + CXCR5 + TFH细胞的频率。结果表明，IA患者CD4 + CXCR5 + TFH细胞比例显著高于IT患者和HC患者，且IA患者CD4 + CXCR5 + TFH比例与AST呈正相关。CHB患者CD4 + CXCR5 + TFH细胞中ICOS+、PD-1+和ICOS + PD-1+细胞比例均显著高于HC患者。阿德福韦酯治疗后IA患者外周血CD4 + CXCR5 + TFH、PD-1 + CD4 + CXCR5 + TFH细胞比例降低，HBsAg、HBeAg浓度降低，而抗HBcAb、HBeAg、IL-2、IFN-γ浓度升高。此外，HBV转基因小鼠脾和肝中CD4 + CXCR5 + TFH细胞的频率高于野生型对照。提示CD4 + CXCR5 + TFH细胞可能参与了HBV相关的免疫应答，CD4 + CXCR5 + TFH细胞的高频率出现可能是评估CHB患者免疫活动期的一个生物标志物。
T follicular helper (TFH) cells are a special subpopulation of T helper cells and can regulate humoral immune responses. This study examined whether the frequency of CD4+CXCR5+ TFH cells could be associated with active immunity in chronic hepatitis B (CHB) patients. The frequencies of peripheral blood CD4+CXCR5+ TFH cells, inducible T cell costimulator (ICOS), and/or programmed death 1 (PD-1) positive CD4+CXCR5+ TFH cells in immune-active (IA), immune-tolerant (IT) CHB, and healthy controls (HC) were characterized by flow cytometry analysis. The effect of adevofir dipivoxil treatment on the frequency of CD4+CXCR5+ TFH cells, the concentrations of serum IL-2, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-21, ALT, AST, HBsAg, HBsAb, HBeAg, HBeAb and HBV loads in IA patients were determined. The potential association of the frequency of CD4+CXCR5+ TFH cells with clinical measures was analyzed. In addition, the frequency of splenic and liver CD4+CXCR5+ TFH cells in HBV-transgenic mice was examined. We found that the frequency of CD4+CXCR5+ TFH cells in IA patients was significantly higher than that of IT patients and HC, and the percentages of CD4+CXCR5+ TFH in IA patients were positively correlated with AST. Furthermore, the percentages of ICOS+, PD-1+, and ICOS+PD-1+ in CD4+CXCR5+ TFH cells in CHB patients were significantly higher than that of HC. Treatment with adefovir dipivoxil reduced the frequency of CD4+CXCR5+ TFH, PD-1+CD4+CXCR5+ TFH cells and the concentrations of HBsAg and HBeAg, but increased the concentrations of HBsAb, HBeAb, IL-2 and IFN-γ in IA patients. Moreover, the frequency of splenic and liver CD4+CXCR5+ TFH cells in HBV-transgenic mice was higher than that of wild-type controls. These data indicate that CD4+CXCR5+ TFH cells may participate in the HBV-related immune responses and that high frequency of CD4+CXCR5+ TFH cells may be a biomarker for the evaluation of active immune stage of CHB patients.
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