肾综合征出血热患者T_H1/T_H2、Tc1/Tc2亚群比例及有关细胞因子变化的研究

The study of T_H1/T_H2 and Tc1/Tc2 balance and cytokine changing in the pathogenesis of hemorrhagic fever with renal syndrome

目的 探讨肾综合征出血热 (HFRS)患者TH1样和TH2样细胞平衡状态以及血清中细胞因子的变化。方法 收集HFRS患者和健康个体血清 ,采用夹心ELISA方法测定IFN γ、IL 4和TNF α的水平。分离PBMC ,采用三色流式细胞术分析HFRS患者CD4 + T细胞和CD8+ T细胞中IFN γ+ 和IL 4 + 细胞的百分率 ,观察HFRS患者TH1 TH2、Tc1 Tc2比例的变化 ,比较了不同病程和病情HFRS患者血清中上述指标的变化。结果 HFRS患者血清中TH1类和TH2类细胞因子水平均明显升高 ,其中IFN γ和IL 4的平均水平显著高于健康个体 (P =0 .0 16 ,P =0 .0 19)。HFRS患者PBMC中TH1、TH2、Tc1、Tc2细胞的平均百分率均高于健康个体 ,Tc细胞比例的改变较TH 细胞明显 ,TH1样细胞的比例较TH2样细胞变化明显。发热期患者血清中IFN γ、IL 4和TNF α的水平明显高于恢复期患者。发热期的重症患者的IFN γ水平升高较轻症明显。结论 HFRS患者血清中IFN γ和IL 4水平以及PBMC中TH1、TH2、Tc1和Tc2细胞的比例均有所升高 ,发热期的患者和重症HFRS患者上述参数变化更明显 。

Objective To investigate the change of T H1 like and T H2 like cells balance and cytokine level in HFRS patients. Methods The levels of IFN γ, IL 4 and TNF α in serum were detected by sandwich ELISA. IFN γ + or IL 4 + T H cells and Tc cells in PBMC from febrile or convalescent phase patients were analyzed by immunofluorescence staining and triple color flow cytometry (FCM) after 4 hour PMA stimulation in vitro . Results The levels of IFN γ, IL 4 and TNF α significantly increased obviously in the serum of HFRS patients. The levels of IFN γ and IL 4 are 13.7 fold and 2.4 fold higher respectively than that of healthy individuals. FCM analysis showed that average percentages of T H1, T H2, Tc1 and Tc2 are 27.8%, 17.5%, 27.6% and 19.6% in PBMC from HFRS patients versus 12.4%, 14.5%, 7.1% and 7.0% in healthy individuals PBMC. The ratios of T H1 to T H2 and Tc1 to Tc2 are 2.10 and 1.70 respectively. The percentages of T H1, T H2, Tc1 and Tc2 in PBMC from febrile phase of severe patients showed more obvious change. Conclusions The levels of IFN γ and IL 4 in serum as well as the percentages of T H1, T H2, Tc1 and Tc2 in PBMC were all increased in HFRS patients especially in febrile phase. It suggested that cellular immunity in HFRS patients is shifted to T H1 type immunity.