HBV感染相关的慢加急性肝衰竭患者外周血中TCR γδT细胞促炎细胞因子的产生及与临床指标的相关性分析

Proinflammatory cytokine production of TCR γδT cells in peripheral blood of patients with HBV-associated acute-on-chronic liver failure,and correlation analysis between cell proportion and clinical parameters

目的探讨HBV感染相关的慢加急性肝衰竭患者(HBV-associated acute-on-chronic liver failure,HBV-ACLF)外周血中TCRγδT(γδT)细胞的比例及产生IFN-γ、TNF-α及IL-17等促炎细胞因子的能力,分析它们与临床指标间的相关性。方法入选26例HBV-ACLF患者、40例慢性HBV感染患者(CHBV)、25例健康对照者,用流式细胞仪方法检测外周血中γδT细胞的频率及产生炎性细胞因子IFN-γ、TNF-α、IL-17细胞的比例,采用SPSS 13.0统计软件分析各组间各细胞比例的差异及细胞比例与临床指标的相关性。结果 HBV-ACLF患者外周血中γδT细胞占总T细胞的比例的中位值为4.8%,低于CHB患者(10.7%)与健康对照者(10.3%),差异有统计学意义(P<0.01)。在体外经刺激后,IFN-γ阳性的γδT细胞在HBV-ACLF组的比例中位值为73.9%、CHBV组为70.9%,高于健康对照组(45.3%,P<0.01);HBV-ACLF患者中TNF-α阳性的γδT细胞中位值为26.7%,显著高于CHBV患者(11.5%)及健康对照组(11.7%,P<0.01);产生IL-17因子的γδT在HBV-ACLF组中中位值为0.7%,高于CHBV组(0.3%)及健康对照组(0.3%,P<0.01)。经Spearman Correlation相关性分析,HBV-ACLF组中TNF-α+γδT细胞的比例与ALT或AST水平呈负相关。结论虽然HBV-ACLF患者外周血中总的γδT细胞比例降低,但产生炎性细胞因子IFN-γ、TNF-α、IL-17的能力显著增强,可能参与了HBV-ACLF发病过程中炎症因子急剧升高的过程。

Objective To explore the proportion of TCR γδT（γδT） cells and the cytokine production ability of the γδT cells in peripheral blood of patients with hepatitis B virus-associated acute-on-chronic liver failure（HBV-ACLF）,and to analyze the correlation between the proportion of cells and the clinical parameters.Methods Twenty-six patients with HBV-ACLF（HBV-ACLF group）,40 patients with chronic HBV infection（CHBV group）,and 25 healthy controls（HC group） were enrolled in this study.The proportion of γδT cells in peripheral blood of the subjects and the proportion of IFN-γ,TNF-α,or IL-17 producing γδT cells were determined by flow cytometry.The differences of the proportion of cytokine-producing γδT cells among the three groups and the correlation of the proportion with clinical parameters were statistically analyzed by SPSS software.Results The proportion of γδT cells in peripheral blood of the HBV-ACLF group（4.8% as median） was significantly lower than that of the CHBV group（10.7% as median） and HC group（10.3% as median）（P0.01）.After stimulation,the proportion of IFN-γ＋ γδT cells in the HBV-ACLF group（73.9% as median） and CHBV group（70.9% as median） was significantly higher than that in the HC group（45.3% as median）（P0.01）.The proportions of TNF-α＋ γδT cells and IL-17＋ γδT cells（26.7% and 0.7% as median） were significantly higher in the HBV-ACLF group than in the CHBV group（11.5% and 0.3%） and HC group（11.7% and 0.3%）（P0.01）.Moreover,the proportion of TNF-α＋ γδT cells was negatively correlated with the levels of ALT and AST.Conclusion Although the proportion of total γδT cells in peripheral blood of HBV-ACLF patients decreases,the ability of the γδT cells in producing IFN-γ,TNF-α and IL-17 is enhanced,which may be involved in the acute systemic inflammatory responses in HBV-ACLF development.