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.
Mol Immunol. 2018 Nov;103:270-278. doi: 10.1016/j.molimm.2018.10.011. Epub 2018 Oct 16.
Given the B helper function of follicular T helper (Tfh) cells and peripheral T helper (Tph) cells, we researched the roles of circulating PD-1CXCR5CD4 T cells and PD-1CXCR5CD4 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-1CXCR5CD4 T cells and PD-1CXCR5CD4 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-1CXCR5CD4 T cells after PEG-IFN-α treatment. In addition, the increase in the frequency of PD-1CXCR5CD4 T cells exerted a significant positive effect on the HBsAg level, which decreased to ≤2 Log IU/mL and ≤3 Log 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-1CXCR5CD4 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-1CXCR5CD4 T cells and PD-1CXCR5CD4 T cells may be involved in the immune landscape of patients with a chronic HBV infection. Moreover, PD-1CXCR5CD4 T cells are associated with decreased HBsAg levels in patients with CHB who are receiving peginterferon-α therapy.
鉴于滤泡辅助性 T 细胞（Tfh）和外周辅助性 T 细胞（Tph）的 B 辅助功能，我们研究了循环 PD-1+CXCR5+CD4+T 细胞和 PD-1+CXCR5+CD4+T 细胞在慢性乙型肝炎（CHB）患者乙型肝炎表面抗原（HBsAg）水平下降和乙型肝炎病毒（HBV）清除中的作用。在本研究中，流式细胞术检测到 CHB 患者 PD-1+CXCR5+CD4+T 细胞和 PD-1+CXCR5+CD4+T 细胞的频率明显高于健康对照（HC）。我们的纵向研究并未显示聚乙二醇干扰素-α（PEG-IFN-α）治疗前 48 周和治疗后两种细胞群的频率有显著差异。然而，重复测量血清 HBsAg 水平显示，在 PEG-IFN-α治疗后 PD-1+CXCR5+CD4+T 细胞频率增加的患者中，HBsAg 水平随时间显著降低。此外，PD-1+CXCR5+CD4+T 细胞频率的增加对 HBsAg 水平有显著的积极影响，使 HBsAg 水平在治疗结束时降至≤2 Log IU/ml 和≤3 Log IU/ml。然而，无论循环 PD-1+CXCR5+CD4+T 细胞的频率是否升高，HBsAg 水平随时间的变化均无显著差异。HBV DNA 浓度的重复测量显示，这两种细胞亚群频率变化与 HBV DNA 清除之间无显著差异。总之，循环 PD-1+CXCR5+CD4+T 细胞和 PD-1+CXCR5+CD4+T 细胞可能参与慢性乙型肝炎感染患者的免疫景观。此外，PD-1+CXCR5+CD4+T 细胞与接受聚乙二醇干扰素-α治疗的 CHB 患者 HBsAg 水平降低相关。
