循环 TFH 细胞及其相关分子的扩增：在慢性乙型肝炎病毒感染患者的免疫景观中的作用。
Expansion of circulating TFH cells and their associated molecules: involvement in the immune landscape in patients with chronic HBV infection.
机构信息
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing 400010, China.
出版信息
Virol J. 2014 Mar 21;11:54. doi: 10.1186/1743-422X-11-54.
BACKGROUND
Blood CXCR5+CD4+ T cells are defined as circulating T follicular helper (TFH) cells, which is required for effective humoral immunity. This study aimed to investigate the role of circulating TFH cells in patients with chronic hepatitis B virus (CHB) infection.
METHODS
The frequency and phenotype of circulating TFH cells were monitored by flow cytometry in CHB patients and in healthy controls (HC). The expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA was analyzed using real-time PCR. Serum HBsAg, HBeAg, HBeAb, HBV DNA loads, ALT and AST were determined. The potential association of the frequency of TFH cells and their surface markers with clinical parameters was assessed.
RESULTS
The frequency of CXCR5+CD4+ T cells was increased in CHB patients and positively correlated with ALT and AST but not with HBV DNA loads. Moreover, an expansion of ICOS-, PD-1-, CD40L-, and IL-21R-expressing TFH cells occurred in CHB patients, but failed to correlate with ALT, AST and HBV DNA loads. Interestingly, the frequency of CXCR5+CD4+ T cells and ICOS+CXCR5+CD4+ T cells was significantly higher in HBeAg positive CHB patients than in HC. Additionally, the percentages of CXCR5+CD4+ T cells were positively correlated with AST, and ICOS-expressing CXCR5+CD4+ T cells were negatively correlated with HBV DNA loads. No significant differences in the frequency of CXCR5+CD4+ T cells were observed between inactive carrier (IC) patients and healthy controls. However, ICOS-, PD-1-, CD40L-expressing TFH cells were increased in IC patients and positively correlated with AST. Furthermore, the expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA in TFH cells was higher in CHB patients than in HC.
CONCLUSIONS
These data demonstrate that circulating TFH cells may participate in HBV-related immune responses. In addition to the frequency of TFH cells, the phenotype of these cells plays an important role in CHB patients.
背景
血液 CXCR5+CD4+T 细胞被定义为循环滤泡辅助性 T 细胞（TFH），这是有效体液免疫所必需的。本研究旨在探讨循环 TFH 细胞在慢性乙型肝炎病毒（CHB）感染患者中的作用。
方法
通过流式细胞术监测 CHB 患者和健康对照者（HC）循环 TFH 细胞的频率和表型。采用实时 PCR 分析 BCL-6、IL-21、IL-4、CXCR5 和 IL-6R mRNA 的表达。检测血清 HBsAg、HBeAg、HBeAb、HBV DNA 载量、ALT 和 AST。评估 TFH 细胞及其表面标志物的频率与临床参数的潜在相关性。
结果
CHB 患者 CXCR5+CD4+T 细胞频率增加，与 ALT 和 AST 呈正相关，但与 HBV DNA 载量无关。此外，CHB 患者中出现了 ICOS-、PD-1-、CD40L-和 IL-21R 表达的 TFH 细胞扩增，但与 ALT、AST 和 HBV DNA 载量无关。有趣的是，HBeAg 阳性 CHB 患者 CXCR5+CD4+T 细胞和 ICOS+CXCR5+CD4+T 细胞的频率明显高于 HC。此外，CXCR5+CD4+T 细胞的百分比与 AST 呈正相关，而 ICOS 表达的 CXCR5+CD4+T 细胞与 HBV DNA 载量呈负相关。IC 患者和 HC 之间 CXCR5+CD4+T 细胞的频率无显著差异。然而，IC 患者中 ICOS-、PD-1-、CD40L 表达的 TFH 细胞增加，并与 AST 呈正相关。此外，CHB 患者 TFH 细胞中 BCL-6、IL-21、IL-4、CXCR5 和 IL-6R mRNA 的表达高于 HC。
结论
这些数据表明，循环 TFH 细胞可能参与 HBV 相关免疫反应。除了 TFH 细胞的频率外，这些细胞的表型在 CHB 患者中也起着重要作用。
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