Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Infect Dis. 2021 Dec 1;224(11):1878-1889. doi: 10.1093/infdis/jiab216.
The immunomodulatory role of natural killer (NK) cells has been recognized recently, but its effects on CD4+CD25+ regulatory T cells (Tregs) during chronic hepatitis B (CHB) infection and treatment remain unclear. A total of 116 nucleos(t)ide analogue (NA)-treated CHB patients were included. An inverse correlation between the peripheral frequencies of NK cells and Tregs was found in NA suppressed patients following pegylated interferon-ɑ (PegIFN-ɑ)-based treatment. Furthermore, NK cells suppressed the proliferation and differentiation of Tregs through secreting IFN-γ as was evidenced in the circulation of NA-treated CHB patients as well as in liver of HBV-carrier mouse model. Additionally, the inhibition could be enhanced by PegIFN-ɑ treatment, which was correlated to more vigorous HBV-specific T-cell responses and marked reduction in HBsAg. Our study reveals a novel immunomodulatory mechanism of NK cells and provides a theoretical basis for PegIFN-ɑ as an immunotherapy agent in treating patients with CHB.
自然杀伤 (NK) 细胞的免疫调节作用最近已得到认可，但在慢性乙型肝炎 (CHB) 感染和治疗过程中，其对 CD4+CD25+调节性 T 细胞 (Tregs) 的影响尚不清楚。共纳入 116 名接受核苷（酸）类似物 (NA) 治疗的 CHB 患者。在接受聚乙二醇干扰素-α (PegIFN-ɑ) 治疗的 NA 抑制患者中，发现外周 NK 细胞和 Tregs 的频率呈负相关。此外，NK 细胞通过分泌 IFN-γ抑制 Tregs 的增殖和分化，这在 NA 治疗的 CHB 患者的循环中以及 HBV 携带者小鼠模型的肝脏中均得到证实。此外，PegIFN-ɑ 治疗可增强抑制作用，这与更强烈的乙型肝炎病毒特异性 T 细胞反应和 HBsAg 的显著减少相关。我们的研究揭示了 NK 细胞的一种新的免疫调节机制，并为 PegIFN-ɑ 作为 CHB 患者免疫治疗药物提供了理论依据。
