Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China.
Department of Hepatology, The First Hospital of Jilin University, Changchun, China.
J Mol Med (Berl). 2019 Mar;97(3):397-407. doi: 10.1007/s00109-018-01735-z. Epub 2019 Jan 21.
Chronic hepatitis C (CHC) is associated with biological activity of T follicular helper (Tfh) cells and memory B cells (MBCs). However, the nature of Tfh cell subsets that are responsible for MBCs in CHC patients has not been evaluated. This study aimed to investigate Tfh and MBC immunity before and after direct-acting antiviral (DAA) therapy in patients with CHC. A total of 31 CHC patients and 15 healthy controls (HCs) were recruited. Individual patients were treated with sofosbuvir/ribavirin (SOF/RBV) or in combination with pegylated interferon alpha-2a (PEG-IFN-α-2a) for 12 weeks. Immunofluorescence revealed the frequency of ICOSCD4CXCR5 active Tfh cells in liver tissue of CHC patients was higher than that of healthy control. Tfh and B cell co-culture experiments showed that Tfh2 cells from CHC patients have potential ability to induce B cell differentiation and IgG production. Flow cytometry showed that the frequencies of CD21CD27IgD activated MBCs, ICOSCD4CXCR5 activated Tfh cells, Tfh1 (IFN-γCD4CXCR5) cells, and Tfh2 (IL-4CD4CXCR5) cells, but not of Tfh17 (IL-17CD4CXCR5) cells, increased in CHC patients before and after DAA therapy. Collectively, ICOS Tfh, Tfh1, Tfh2 cells, and MBCs participated in the antiviral treatment process of SOF/RBV with or without PEG-IFN-α-2a in CHC patients, and their activity was further enhanced during the treatment. KEY MESSAGES: This study aimed to investigate Tfh cells and MBC immunity in CHC patients. CD21CD27IgD activated MBCs increased in CHC patients before and after treatment. Tfh1 and Tfh2 cells increased in CHC patients before and after antiviral treatment. Intrahepatic activated Tfh cells increased in CHC patients before treatment. Tfh2 cells from CHC patients have a stronger ability to induce B cell differentiation.
慢性丙型肝炎（CHC）与滤泡辅助性 T 细胞（Tfh）和记忆 B 细胞（MBC）的生物活性有关。然而，负责 CHC 患者 MBC 的 Tfh 细胞亚群的性质尚未得到评估。本研究旨在探讨 CHC 患者接受直接作用抗病毒（DAA）治疗前后的 Tfh 和 MBC 免疫。共招募了 31 名 CHC 患者和 15 名健康对照（HC）。个别患者接受索非布韦/利巴韦林（SOF/RBV）或联合聚乙二醇干扰素α-2a（PEG-IFN-α-2a）治疗 12 周。免疫荧光显示，CHC 患者肝组织中 ICOSCD4CXCR5 活性 Tfh 细胞的频率高于健康对照。Tfh 和 B 细胞共培养实验表明，CHC 患者来源的 Tfh2 细胞具有潜在诱导 B 细胞分化和 IgG 产生的能力。流式细胞术显示，CD21CD27IgD 激活的 MBC、ICOSCD4CXCR5 激活的 Tfh 细胞、Tfh1（IFN-γCD4CXCR5）细胞和 Tfh2（IL-4CD4CXCR5）细胞的频率，而不是 Tfh17（IL-17CD4CXCR5）细胞，在 CHC 患者 DAA 治疗前后均增加。总之，在 CHC 患者中，SOF/RBV 联合或不联合 PEG-IFN-α-2a 的抗病毒治疗过程中，ICOS Tfh、Tfh1、Tfh2 细胞和 MBC 参与其中，其活性在治疗过程中进一步增强。关键信息：本研究旨在探讨 CHC 患者的 Tfh 细胞和 MBC 免疫。CD21CD27IgD 激活的 MBC 在 CHC 患者治疗前后增加。Tfh1 和 Tfh2 细胞在 CHC 患者抗病毒治疗前后增加。CHC 患者治疗前肝内激活的 Tfh 细胞增加。CHC 患者来源的 Tfh2 细胞具有更强的诱导 B 细胞分化的能力。
