在e抗原阳性慢性乙型肝炎患者恢聚乙二醇干扰素α增强恢复

StephenW

http://www.virologyj.com/content/9/1/274/abstract

在e抗原阳性慢性乙型肝炎患者恢聚乙二醇干扰素α增强恢复记忆性T细胞
Pegylated interferon alpha enhances recovery of memory T cells in e antigen positive chronic hepatitis B patients

Yong Zhe Liu, Feng Qin Hou, Peng Ding, Yuan Yuan Ren, Shi Hong Li and Gui Qiang Wang   


Virology Journal 2012, 9:274 doi:10.1186/1743-422X-9-274
Published: 16 November 2012
Abstract (provisional)
Background

Interferons (IFNs) are a group of cytokines commonly used in the clinical treatment of chronic hepatitis B (CHB) patients. Their therapeutic effects are highly correlated with recovery of host antiviral immunity. Clearance of hepatitis B virus (HBV) is mediated partially by activated functional memory T cells. The aims of the present study were to investigate memory T cell status in patients with different outcomes following pegylated interferon-alpha (IFN-alpha) therapy and to identify new biomarkers for predicting antiviral immune responses.
Methods

Peripheral blood cells were isolated from 23 CHB patients who were treated with pegylated IFN-alpha at week 0 (baseline) and week 24. Co-expression of programmed death-1 (PD-1) and CD244 in CD45RO positive T cells, as well as a subset of CD127 and CXCR4 positive memory T cells were assessed. In addition, perforin, granzyme B, and interferon-gamma (IFN-gamma) expressions were also analyzed by flow cytometric analysis after intracytoplasmic cytokine staining (ICCS). Peripheral blood mononuclear cells (PBMC) isolated at week 24 were re-challenged with exogenous HBV core antigen, and the percentage of IFN-gamma expression, serum HBV DNA loads, and ALT (alanine aminotransferase) levels were evaluated.
Results

At week 24, PD-1 and CD244 expression in CD8 memory T cells were down-regulated (P < 0.05,P < 0.05, respectively), along with decreased HBV DNA loads (P < 0.05), while the expressions of partial effector molecules in CD8 and CD4 memory T cells was up-regulated (P < 0.05,P < 0.05, respectively), especially in the responders. CD127 and CXCR4 were highly expressed in CD8 memory T cells after pegylated IFN-alpha treatment (P < 0.05), which was inversely correlated with HBV DNA loads (r = -0.47, P = 0.001). The responders had a higher IFN-gamma expression in memory T cells than the non-responders did after HBV antigen re-stimulation in vitro.
Conclusion

Pegylated IFN-alpha treatment enhanced recovery of memory T cells in CHB patients by down-regulating inhibitory receptors and up-regulating effector molecules. The expressions of CXCR4 and CD127 in CD8 memory T cell may be used as biomarkers for predicting the outcome of treatment.

StephenW

摘要（临时）
背景

干扰素（IFNs）是一组慢性乙型肝炎（CHB）患者的临床治疗中常用的细胞因子。他们高度相关的恢复宿主抗病毒免疫治疗效果。部分被激活的功能性记忆性T细胞介导的​​B型肝炎病毒（HBV）的间隙。本研究的目的是调查不同的结果，聚乙二醇化干扰素-α（IFN-α）治疗后患者的记忆性T细胞的状态，并确定新的生物标志物用于预测抗病毒免疫反应。
方法

在0周（基线）和24周的聚乙二醇化干扰素-α治疗23例慢性乙型肝炎患者外周血单个核细胞中分离出。共表达的程序性死亡1（PD-1）和CD244在CD45RO阳性​​T细胞，以及一个子集，CD127和CXCR4阳性记忆T细胞进行了评估。此外，穿孔素，颗粒酶B，和γ-干扰素（IFN-γ）的表达进行了分析，流式细胞仪分析后，卵胞浆内细胞因子染色（ICCS）。外周血单核细胞（PBMC），在第24周中分离重新挑战与外源性HBV核心抗原，和IFN-γ的表达百分比，血清HBV DNA负载，和ALT（丙氨酸氨基转移酶）的水平进行了评价。
结果

在第24周，PD-1和CD8记忆T细胞的CD244表达的下调（P <0.05，P <0.05），以及降低HBV DNA载量（P <0.05），而局部效应分子的表达CD8和CD4记忆T细胞上调（P <0.05，P <0.05），尤其是在响应。 CD127和CXCR4了，CD8记忆T细胞中高表达后，聚乙二醇化干扰素-α治疗（P <0.05），HBV DNA载量相关（r = -0.47，P = 0.001）呈负相关。响应者有较高的记忆性T细胞中的IFN-γ的表达比非应答者HBV抗原在体外再刺激后所做的。
结论

聚乙二醇化干扰素-α治疗提高采收率的记忆性T细胞在慢性乙型肝炎患者通过下调抑制性受体和上调的效应分子。 CXCR4和CD127 CD8记忆T细胞中的表达，也可以使用作为生物标志物用于预测的治疗结果。