慢性丙型肝炎患者外周血髓系来源抑制细胞增加与病毒复制的相关性

Increased myeloid-derived suppressor cells correlate with viral persistence in patients with chronic hepatitis C

目的:分析慢性丙型肝炎(chronic hepatitis C,CHC)患者外周血髓系来源抑制细胞(myeloidderived suppressor cells,MDSCs)的特征及其与病毒复制的关系.方法:采用流式细胞术检测了61例CHC患者[包括14例快速病毒学应答(rapid virological response,RVR)患者、22例早期病毒学应答患者(early virological response,EVR)]和25例健康对照(healthy control,HC)的外周血MDSCs频率,并分析其与临床病毒载量和肝脏生化指标之间的相关性.结果:基线水平CHC组MDSCs的频率高于健康组(1.33%vs 0.7%,P<0.001),且与HCV RNA载量呈正相关(r=0.636,P<0.001),与谷丙转氨酶水平无关(r=0.156,P=0.229);CD8 T细胞表面的T细胞受体(T cell receptor,TCR)ζ链表达降低与CHC组MDSCs频率升高呈负相关(r=0.690,P<0.001),在体外加入L-精氨酸可使其恢复;抗病毒治疗后,MDSCs频率呈下降趋势,且RVR组基线水平的MDSCs频率高于EVR组(P=0.024).结论:CHC患者外周血MDSCs频率升高可能通过下调CD8 TCRζ链表达抑制机体的抗病毒应答,从而引起病毒的复制,抗病毒治疗可使CD8 TCRζ链的表达部分恢复.

AIM： To investigate the characteristics and clinical significance of myeloid-derived suppressor cells （MDSCs） in patients with chronic hepatitis C （CHC）. METHODS： The frequencies and phenotypes of peripheral blood MDSCs were analyzed in 61 patients with CHC, including 14 rapid virological response （RVR） cases and 22 early virological response （EVR） cases, and 25 healthy controls （HC）. The correlations between the characteristics of MDSCs and clinical markers were analyzed. RESULTS： The frequencies of peripheral MDSCs in CHC patients at baseline were significantly higher than those in the HC group （1.33% vs 0.7%, P 〈 0.001）, which were positively correlated with HCV RNA load （r = 0.636, P 〈 0.001）. T cell receptor （TCR） ζ expression on CD8 T cells was negatively correlated with the frequencies of MDSCs in CHC patients at baseline （r = 0.690, P 〈 0.001）, and could be restored by L-arginine in vitro. The frequencies of MDSCs decreased after antiviral therapy, which were higher in the RVR group than in the EVR group （P = 0.024）. TCR ζ expression on CD8 T cells increased in both RVR and EVR cases.CONCLUSION： In CHC patients, MDSCs may suppress immune response by down-regulating TCR ζ expression on CD8 T cells, resulting in viral persistence.