T 滤泡辅助细胞通过促进 HBsAb 的产生来改善慢性乙型肝炎患

StephenW

T 滤泡辅助细胞通过促进 HBsAb 的产生来改善慢性乙型肝炎患者对干扰素的反应

    Yong Liu, Xintong Hu, Xiaoli Hu, Lei Yu, Huifan Ji, Wanyu Li, Yanjun Cai, Genhong Cheng & Yanfang Jiang

胃肠病学杂志第 57 卷，第 30-45 页（2022 年）引用这篇文章

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抽象的
背景和目标

乙型肝炎表面抗原 (HBsAg) 血清转换被认为是治疗慢性乙型肝炎病毒 (HBV) 感染的最佳结果。在这项研究中，我们旨在确定聚乙二醇干扰素α (PEG-IFN-α) 提高慢性乙型肝炎 (CHB) 患者血清转化率的细胞和分子机制。
方法

使用来自 15 名健康个体和 45 名 CHB 患者的循环滤泡辅助 T (TFH) 细胞进行流式细胞术，这些患者对PEG-IFN-α 单一疗法的标准 48 周方案，以检查循环 TFH 细胞在 CHB 患者对 PEG-IFN-α 的治疗反应中的意义。此外，通过进行共培养实验评估了不同 TFH 亚群激活 B 细胞和刺激 IgG 产生的能力。
结果

纵向分析显示，与 NRG 和 ICRG 相比，CRG 中 CD40L+CD4+CXCR5+ TFH 细胞的数量特异性显着增加。根据体外共培养实验的结果，阻断 CD40-CD40L 信号，而不是 ICOS-ICOSL 信号，特异性抑制 B 细胞活化和 IgG 产生。 HBV 可能通过增强抑制性调节性 T 细胞活性来损害 TFH 细胞功能。转录组分析进一步揭示了从 CRG 分离的 TFH 细胞中 CD40L 的上调，而不是 ICOS 的上调。
结论

TFH 细胞，尤其是那些表达 CD40L 的细胞，可刺激 B 细胞分化并提高接受 PEG-IFN-α 单药治疗的 CHB 患者的 HBsAg 血清转化率。

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缩写

AHB：

    慢性活动性乙型肝炎
AHC：

    慢性无症状HBV携带者
中央银行：

    细胞计数珠阵列
慢性乙型肝炎：

    慢性乙型肝炎
中铁：

    完整响应组
乙肝病毒：

    乙型肝炎病毒
乙肝表面抗原：

    乙型肝炎表面抗原
HBsAb：

    抗-HBs抗体
慧聪：

    健康控制
ICRG：

    不完整的响应组
NRG：

    未答复组
PBMC：

    外周血单个核细胞
PD-1：

    程序性细胞死亡蛋白 1
PEG-IFN-α：

    聚乙二醇干扰素α
TFH:

    T卵泡助手

StephenW

T follicular helper cells improve the response of patients with chronic hepatitis B to interferon by promoting HBsAb production

    Yong Liu, Xintong Hu, Xiaoli Hu, Lei Yu, Huifan Ji, Wanyu Li, Yanjun Cai, Genhong Cheng & Yanfang Jiang

Journal of Gastroenterology volume 57, pages 30–45 (2022)Cite this article

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Abstract
Background and aims

Hepatitis B surface antigen (HBsAg) seroconversion is considered the optimal outcome of the treatment of chronic hepatitis B virus (HBV) infection. In this study, we aimed to determine the cellular and molecular mechanisms by which pegylated interferon alpha (PEG-IFN-α) improves the seroconversion rate in patients with chronic hepatitis B (CHB).
Methods

Flow cytometry was performed using circulating T follicular helper (TFH) cells from 15 healthy individuals and 45 patients with CHB presenting different treatment responses [complete response group (CRG), incomplete response group (ICRG), and nonresponse group (NRG)] to the standard 48-week regimen of PEG-IFN-α monotherapy to examine the significance of circulating TFH cells in the therapeutic response of patients with CHB to PEG-IFN-α. In addition, the capacities of different TFH subsets to activate B cells and stimulate IgG production were assessed by performing coculture experiments.
Results

Longitudinal analysis revealed specific and significant increases in the numbers of CD40L+CD4+CXCR5+ TFH cells in the CRG compared with the NRG and ICRG. According to the results of in vitro coculture experiments, blocking CD40-CD40L signaling, but not ICOS–ICOSL signaling, specifically inhibits B-cell activation and IgG production. HBV may impair TFH cell function by enhancing inhibitory regulatory T-cell activity. Transcriptome analysis further revealed the upregulation of CD40L, but not of ICOS, in TFH cells isolated from the CRG.
Conclusions

TFH cells, particularly those with CD40L expression, stimulate B-cell differentiation and improve the HBsAg seroconversion rate in patients with CHB treated with PEG-IFN-α monotherapy.

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Abbreviations

AHB:

    Chronic active hepatitis B
AHC:

    Chronic asymptomatic HBV carriers
CBA:

    Cytometric bead array
CHB:

    Chronic hepatitis B
CRG:

    Complete response group
HBV:

    Hepatitis B virus
HBsAg:

    Hepatitis B surface antigen
HBsAb:

    Anti-HBs antibody
HC:

    Healthy control
ICRG:

    Incomplete response group
NRG:

    Nonresponse group
PBMC:

    Peripheral blood mononuclear cell
PD-1:

    Programmed cell death protein 1
PEG-IFN-α:

    Pegylated interferon alpha
TFH:

    T follicular helper

StephenW

https://link.springer.com/conten ... 535-021-01840-w.pdf