辅助性T细胞极化群体在慢性乙型肝炎病毒感染中的作用

Polarized populations of T helper cells in patients with chronic hepatitis B virus infection

目的 了解慢性乙型肝炎病毒 (HBV)感染者外周血中辅助性T细胞 (Th)内干扰素 γ(IFN γ)、白细胞介素 4(IL 4)、和转化生长因子 β(TGF β)的表达情况 ,以测定Th1/Th2 /Th3细胞的百分率 ,探明Th细胞各极化群体在慢性HBV感染中的作用。方法 将 36例慢性HBV感染者分 2组 ,慢性HBV感染组和中度慢性乙型肝炎组 ,每组 18例患者。正常对照组 12名。常规分离外周血单个核细胞 (PBMC) ,在佛波二脂 (PMA)、钙离子导入剂伊屋诺霉素 (ionomycin)、细胞内转运阻断剂莫能星(Monensin)的刺激下 ,采用流式细胞分析术 (FACS)对慢性HBV感染者外周血单个Th细胞内IL 4、IFN γ和TGF β的表达进行分析。 结果 正常对照组 ,2 .3%～ 18.6 %的CD4+T细胞为Th1细胞 ,0 .9%～9.2 %为Th2细胞 ;0 .7%～ 7.1%的细胞仅表达TGF β,为Th3细胞。在慢性HBV感染者外周血单个CD4+T细胞中 ,以Th0细胞居多 ;而Th1细胞则随着慢性乙型肝炎肝脏炎症活动的加剧而明显增多 ,在炎症活动明显的慢性乙型肝炎 ,其Th1百分数明显高于炎症活动呈静止状态的慢性乙型肝炎 ;Th2细胞在慢性HBV感染的不同阶段则较为恒定 (P >0 .0 5 ) ,但明显高于对照组 (P <0 .0 5 )。Th3细胞的百分率则随着肝组织炎症活动的加剧 ,其比例也明显减少 (P <0 .0 5 ) ,在无症状?

Objectives To investigate the composition of Th1/Th2/Th3 cells in chronic HBV infected individuals by determining the expression of IL 4/IFN γ/TGF β in single CD4+ T cell isolated from the peripheral blood mononuclear cells (PBMCs), and analyze the role of Th cells polarized population in chronic HBV infection. Methods PBMCs from chronic HBV infected individuals were separated routinely, stimulated by PMA/Ionomycin/Monensin, and the production of IL 4/IFN γ/TGF β by CD4+ T cells in PBMCs was determined by FACS analysis. Results The percentage of IFN γ producing T cells, IL 4 producing T cells and TGF β producing T cells ranged from 2.3%～18.6%, 1.1%～8.7% and 0.7%～7.1%, respectively, in CD4+ cells from non infected individuals. The majority of CD4+ T cells from PBMCs in chronic HBV infected individuals were Th0 cells. The proportion of Th1 cells increased significantly with the hepatic inflammation activity, and the proportion in active period of chronic hepatitis B was higher than that in nonactive period ( P <0.05). The percentage of Th2 cells in CD4+ T cells from HBV infected individuals did not differ significantly ( P >0.05), but it was higher than controls ( P <0.05). The percentage of Th3 cells in CD4+ T cells from AsC group was higher than that in CHB group and control ( P <0.05). Conclusions Th1 phenotype cytokines are correlated with hepatic inflammation activity of chronic hepatitis B. Th2 cells may be associated with the persistence of HBV infection. Th3 cells cooperating with Th2 cells exert negative immunoregulating action and may be associated with the immune tolerance state of chronic HBV infection.