循环PD-1hiCXCR5 + CD4 + T细胞与接受聚乙二醇干扰素-α治疗的慢

StephenW

Mol Immunol. 2018 Oct 16;103:270-278. doi: 10.1016/j.molimm.2018.10.011. [Epub ahead of print]
Circulating PD-1hiCXCR5+CD4+ T cells are associated with a decrease in hepatitis B surface antigen levels in patients with chronic hepatitis B who are receiving peginterferon-α therapy.
Zhang L1, Li H2, Ren H3, Hu P4.
Author information

1
    Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
2
    Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
3
    Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
4
    Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].

Abstract

Given the B helper function of follicular T helper (Tfh) cells and peripheral T helper (Tph) cells, we researched the roles of circulating PD-1hiCXCR5+CD4+ T cells and PD-1hiCXCR5-CD4+ T cells in the decrease in hepatitis B surface antigen (HBsAg) levels and hepatitis B virus (HBV) clearance in patients with chronic hepatitis B (CHB). In the present study, the frequencies of PD-1hiCXCR5+CD4+ T cells and PD-1hiCXCR5-CD4+ T cells measured by flow cytometry were significantly higher in patients with CHB than that in healthy controls (HCs). Our longitudinal study did not reveal significant differences in the frequencies of both cell populations before and after 48 weeks of peginterferon-α (PEG-IFN-α) therapy. However, repeated measurements of serum HBsAg levels revealed significantly lower HBsAg levels over time in patients who exhibited an increase in the frequency of PD-1hiCXCR5+CD4+ T cells after PEG-IFN-α treatment. In addition, the increase in the frequency of PD-1hiCXCR5+CD4+ T cells exerted a significant positive effect on the HBsAg level, which decreased to ≤2 Log10 IU/mL and ≤3 Log10 IU/mL at the end of treatment. However, no significant difference in HBsAg levels was observed over time, regardless of whether the frequency of circulating PD-1hiCXCR5-CD4+ T cells was elevated. Repeated measurements of the HBV DNA concentration did not show significant differences between patients exhibiting changes in the frequencies of these two cell subsets and HBV DNA clearance. Overall, circulating PD-1hiCXCR5+CD4+ T cells and PD-1hiCXCR5-CD4+ T cells may be involved in the immune landscape of patients with a chronic HBV infection. Moreover, PD-1hiCXCR5+CD4+ T cells are associated with decreased HBsAg levels in patients with CHB who are receiving peginterferon-α therapy.
KEYWORDS:

Follicular T helper cells; Hepatitis B surface antigen; Hepatitis B virus; PD-1; Peginterferon-α; Peripheral T helper cells

PMID:
    30340072
DOI:
    10.1016/j.molimm.2018.10.011

StephenW

Mol Immunol。 2018年10月16日; 103：270-278。 doi：10.1016 / j.molimm.2018.10.011。 [提前打印]
循环PD-1hiCXCR5 + CD4 + T细胞与接受聚乙二醇干扰素-α治疗的慢性乙型肝炎患者的乙型肝炎表面抗原水平降低有关。
Zhang L1，Li H2，Ren H3，Hu P4。
作者信息

1
    中国重庆医科大学附属第二医院中国教育部传染病分子生物学重点实验室病毒性肝炎研究所传染病研究室，重庆电子地址：[email protected]。
2
    中国重庆医科大学附属第二医院中国教育部传染病分子生物学重点实验室病毒性肝炎研究所传染病研究室，重庆电子地址：[email protected]。
3
    中国重庆医科大学附属第二医院中国教育部传染病分子生物学重点实验室病毒性肝炎研究所传染病研究室，重庆电子地址：[email protected]。
4
    中国重庆医科大学附属第二医院中国教育部传染病分子生物学重点实验室病毒性肝炎研究所传染病研究室，重庆电子地址：[email protected]。

抽象

鉴于卵泡T辅助细胞（Tfh）和外周T辅助细胞（Tph）的B辅助功能，我们研究了循环PD-1hiCXCR5 + CD4 + T细胞和PD-1hiCXCR5-CD4 + T细胞在乙型肝炎表面减少中的作用。慢性乙型肝炎（CHB）患者的抗原（HBsAg）水平和乙型肝炎病毒（HBV）清除率。在本研究中，通过流式细胞术测量的PD-1hiCXCR5 + CD4 + T细胞和PD-1hiCXCR5-CD4 + T细胞的频率在CHB患者中显着高于健康对照（HC）。我们的纵向研究未发现聚乙二醇干扰素-α（PEG-IFN-α）治疗48周前后两种细胞群的频率存在显着差异。然而，重复测量血清HBsAg水平显示，在PEG-IFN-α处理后表现出PD-1hiCXCR5 + CD4 + T细胞频率增加的患者中HBsAg水平随时间显着降低。此外，PD-1hiCXCR5 + CD4 + T细胞频率的增加对HBsAg水平产生显着的积极作用，其在治疗结束时降至≤2Log10IU/ mL和≤3Log10IU/ mL。然而，无论循环PD-1hiCXCR5-CD4 + T细胞的频率是否升高，均未观察到HBsAg水平随时间的显着差异。 HBV DNA浓度的重复测量未显示出表现出这两种细胞亚群频率变化和HBV DNA清除率的患者之间的显着差异。总体而言，循环PD-1hiCXCR5 + CD4 + T细胞和PD-1hiCXCR5-CD4 + T细胞可能参与慢性HBV感染患者的免疫情况。此外，PD-1hiCXCR5 + CD4 + T细胞与接受聚乙二醇干扰素-α治疗的CHB患者的HBsAg水平降低有关。
关键词：

卵泡T辅助细胞;乙型肝炎表面抗原;乙型肝炎病毒; PD-1;聚乙二醇干扰素-α;外周T辅助细胞

结论：
    30340072
DOI：
    10.1016 / j.molimm.2018.10.011

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