Su Shan-shan, He Huan, Kong Ling-bo, Zhang Yu-guo, Zhao Su-xian, Wang Rong-qi, Zheng Huan-wei, Sun Dian-xing, Nan Yue-min, Yu Jun
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Infectious Disease, The Fifth Hospital of Shijiazhuang City, Shijiazhuang, China.
PLoS One. 2014 Apr 7;9(4):e93620. doi: 10.1371/journal.pone.0093620. eCollection 2014.
BACKGROUND & AIMS: The cellular immunity has a profound impact on the status of hepatitis C virus (HCV) infection. However, the response of cellular immunity on the virological response in patients with antiviral treatment remains largely unclear. We aimed to clarify the response of peripheral T cells and monocytes in chronic hepatitis C patients with antiviral treatment.
Patients with chronic hepatitis C were treated either with interferon alpha-2b plus ribavirin (n = 37) or with pegylated interferon alpha-2a plus ribavirin (n = 33) for up to 24 weeks. Frequencies of peripheral regulatory T-cells (Tregs), programmed death-1 (PD-1) expressing CD4+ T-cells or CD8+ T-cells and toll-like receptor (TLR) 3 expressing CD14+ monocytes were evaluated by flow cytometry in patients at baseline, 12 and 24 weeks following treatment and in 20 healthy controls.
Frequencies of Tregs, PD-1 and TLR3 expressing cells were higher in patients than those in control subjects (P<0.05). Patients with complete early virological response (cEVR) showed lower Tregs, PD-1 expressing CD4+ or CD8+ T-cells than those without cEVR at 12 weeks (P<0.05). Patients with low TLR3 expressing CD14+ monocytes at baseline had a high rate of cEVR (P<0.05).
Low peripheral TLR3 expressing CD14+ monocytes at baseline could serve as a predictor for cEVR of antiviral therapy in chronic HCV-infected patients. The cEVR rates were significantly increased in the patients with reduced circulating Tregs, PD-1 expressing CD4+ or CD8+ T-cells.
Chinese Clinical Trial Registry ChiCTR10001090.
细胞免疫对丙型肝炎病毒（HCV）感染状态有深远影响。然而，抗病毒治疗患者中细胞免疫对病毒学应答的反应仍不清楚。我们旨在阐明慢性丙型肝炎患者抗病毒治疗时外周血T细胞和单核细胞的反应。
慢性丙型肝炎患者分别接受α-2b干扰素联合利巴韦林治疗（n = 37）或聚乙二醇化α-2a干扰素联合利巴韦林治疗（n = 33），疗程长达24周。采用流式细胞术评估基线、治疗12周和24周时患者以及20名健康对照者外周调节性T细胞（Tregs）、表达程序性死亡-1（PD-1）的CD4⁺ T细胞或CD8⁺ T细胞以及表达Toll样受体（TLR）3的CD14⁺单核细胞的频率。
患者中Tregs、PD-1和表达TLR3的细胞频率高于对照者（P<0.05）。完全早期病毒学应答（cEVR）患者在12周时的Tregs、表达PD-1的CD4⁺或CD8⁺ T细胞低于无cEVR的患者（P<0.05）。基线时表达TLR3的CD14⁺单核细胞水平低的患者cEVR率高（P<0.05）。
基线时外周血表达TLR3的CD14⁺单核细胞水平低可作为慢性HCV感染患者抗病毒治疗cEVR的预测指标。循环Tregs、表达PD-1的CD4⁺或CD8⁺ T细胞减少的患者cEVR率显著升高。
中国临床试验注册中心ChiCTR10001090
