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慢性乙型和丙型肝炎病毒合并感染患者调节性 T 细胞功能的特征。

Characteristics of regulatory T-cell function in patients with chronic hepatitis B and C coinfection.

机构信息

Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.

School of Medicine, Tzuchi University, Hualien, Taiwan.

出版信息

J Viral Hepat. 2020 Aug;27(8):800-809. doi: 10.1111/jvh.13298. Epub 2020 Apr 14.

Abstract

Regulatory T cells (Tregs) affect the pathogenesis and disease progression of chronic viral hepatitis. This study evaluated the frequency and function of Tregs in patients with chronic HBV/HCV coinfection. Seventy-four untreated HBV/HCV co-infected patients were enrolled in this study. These subjects were divided into four subgroups: HBV-active/HCV-active (BACA), HBV-inactive/HCV-active (BICA), HBV-active/HCV-inactive (BACI) and HBV-inactive/HCV-inactive (BICI). Treg frequency was calculated as the fraction of CD4 Foxp3 T cells among CD4 T cells. Treg-mediated inhibition was measured as percent of inhibition of T-cell proliferation. The expression of interferon (IFN)-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-10 with/without Treg inhibition was also studied. Among the patients, there were 8 cases of BACA (10.8%), 38 of BICA (51.4%), 14 of BACI (18.9%) and 14 of BICI (18.9%). The frequency of CD4 Foxp3 T cells was comparable between the four groups. The inhibitory function of Tregs among the patients in the BACA and BICA was higher than that in the BICI (BACA vs BICI, P = .0210; BICA vs BICI, P = .0301). Patients in the BACA and BICA had higher fibrosis-4 (FIB-4) scores and serum ALT levels and lower serum albumin levels than those of the other groups. ALT abnormality was significantly and independently associated with a higher Treg immunosuppressive ability. The IFN-γ expression of the effector T cells in the BACA was higher than that of the other groups. In conclusion, the inhibitory function of Tregs is higher among the HBV/HCV co-infected patients with active HCV infection. ALT abnormality plays a dominant role in Treg function.

摘要

调节性 T 细胞(Tregs)影响慢性病毒性肝炎的发病机制和疾病进展。本研究评估了慢性 HBV/HCV 合并感染患者 Tregs 的频率和功能。本研究纳入了 74 例未经治疗的 HBV/HCV 合并感染患者。这些患者被分为四组:HBV 活跃/HCV 活跃(BACA)、HBV 不活跃/HCV 活跃(BICA)、HBV 活跃/HCV 不活跃(BACI)和 HBV 不活跃/HCV 不活跃(BICI)。Treg 频率计算为 CD4 Foxp3 T 细胞在 CD4 T 细胞中的分数。Treg 介导的抑制作用通过 T 细胞增殖抑制的百分比来衡量。还研究了 IFN-γ、TNF-α 和 IL-10 的表达,以及有无 Treg 抑制时的表达。在患者中,有 8 例为 BACA(10.8%)、38 例为 BICA(51.4%)、14 例为 BACI(18.9%)和 14 例为 BICI(18.9%)。四组患者的 CD4 Foxp3 T 细胞频率相似。BACA 和 BICA 患者的 Treg 抑制功能高于 BICI(BACA 与 BICI 比较,P=0.0210;BICA 与 BICI 比较,P=0.0301)。BACA 和 BICA 患者的 FIB-4 评分、血清 ALT 水平较高,血清白蛋白水平较低,与其他组相比差异有统计学意义。ALT 异常与 Treg 免疫抑制能力的升高显著相关,且独立相关。BACA 患者效应 T 细胞的 IFN-γ 表达高于其他组。总之,HBV/HCV 合并感染患者中,HCV 活跃感染患者的 Tregs 抑制功能较高。ALT 异常在 Treg 功能中起主导作用。

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