不同临床类型的HBV感染者外周血T淋巴细胞STAT信号表达的研究

Study on the expression of STAT signaling in T lymphocytes of peripheral blood from patients infected with HBV in different clinical types

目的研究不同临床类型HBV感染者外周血T细胞表达细胞因子水平与细胞因子受体信号蛋白(STATs)活性间的关系。方法检测慢性乙肝(CHB)、慢性重型肝炎(CSH)、健康携带者(AsC)以及健康者T细胞表达IFN-γ、IL-12、IL-10、IL-4含量及细胞内STAT-1、3、4、5、6活性。结果 CHB、CSH及AsC细胞因子水平普遍上升(P<0.001或0.01)。IL-10、IL-12受体信号STAT3和STAT4活性与细胞因子水平一致;IFN-γ、IL-4受体信号STAT1、STAT6活性与细胞因子水平不一致,不同个体间差异较大。结论不同临床类型的HBV感染者T细胞表达Th1型和Th2型细胞因子普遍增强,细胞内STATs活性与细胞因子含量不完全一致,细胞内STATs活性存在个体差距。

Objective To detect the relationship of cytokine levels in T cells of blood from patients infected with HBV in different clinical types with the expression of signaling molecules of signal transducers and activators of transcription（STAT1,3,4,5,6） in T cells.Methods T cells were separated from healthy volunteers and the following patients infected with HBV： chronic hepatitis B（CHB）,chronic severe hepatitis（CSH） and asymptomatic HBsAg carriers（AsC）.Cytokine concentrations of Th1 type（IFN-γ,IL-12） and Th2 type（IL-10,IL-4） in culture supernatant of the above T cells were detected and activities of STAT（1,3,4,5,6） were detected by Western blot assay.Results Compared with healthy volunteers,cytokine levels of T cells from AsC were increased in relatively little degree and there was no obvious difference for IFN-γ.In contrast,concentrations of IFN-γ,IL-12,IL-10 and IL-4 expressed by T cells from CHB and CSH were increased significantly（P0.001 or 0.01）.Different from IFN-γ levels in culture supernatant,activities of STAT1 for IFN-γ receptor in T cells from patients of different clinical types were similar to that of healthy volunteers.However,compared with healthy volunteers,signaling activities of STAT3 and STAT4 for IL-10 and IL-12 receptors respectively were consistent to the corresponding cytokine levels in patients of different clinical types.Different from IL-4,activities of STAT6 for IL-4 receptor in T cells from HBV infecting patients also appeared no obvious difference compared with healthy volunteers,but there existed significant difference among patients of the same clinical type.Conclusion Cytokine expression levels of Th1 and Th2 types of T cells from patients infected with HBV in different clinical types are increased in different degrees.In contrast,signaling molecule activities of cytokine receptors STAT（1,3,4,5,6） in T cells from patients of different clinical types might exist obvious differences compared with corresponding cytokine levels.It also exits significant difference about activities of STAT（1,3,4,5,6） among patients of same clinical type.