CD_4^+CD_(25)^+Foxp3^+调节性T细胞在乙型肝炎病毒感染慢性化中的作用

Studies on effect of CD_4^+CD_(25)^+Foxp3^+ regulatory T cells in chronic hepatitis B virus infection

目的探讨CD4+CD25+Foxp3+调节性T细胞(Treg)在慢性乙型肝炎病毒(HBV)感染中的免疫调节作用,分析HBV感染的慢性化是否与外周血中CD4+CD25+Foxp3+调节性T细胞的表达率有关。方法本院2008年6月—2009年5月收治的HBV感染者60例,其中乙型肝炎活动期患者30例,HBV携带者30例,选择同期门诊体检者30例为对照者。应用流式细胞仪检测外周血CD4+CD25+Foxp3+调节性T细胞表达,结合HBV感染者临床情况分析各组外周血中CD4+CD25+Foxp3+调节性T细胞的比率与血清HBeAg和HBVDNA含量的关系。结果 HBV感染及HBV携带者外周血CD4+CD25+Foxp3+调节性T细胞表达率较健康对照组显著增高[(8.68%±1.23)%与(1.38±0.6)4%,P<0.01];慢性乙肝携带组与慢性乙肝恢复组比较,外周血CD4+CD25+Foxp3+调节性T细胞的表达率差异有统计学意义[(8.68±1.23)%与(2.63±1.38)%,P<0.01];HBVDNA病毒含量及HBeAg含量与外周血CD4+CD25+Foxp3+调节性T细胞的表达率之间存在正相关(P<0.01)。结论 HBV感染者外周血CD4+CD25+Foxp3+调节性T细胞水平与疾病进展明显相关,Treg在慢性乙型肝炎携带者中明显增高,并与病毒载量相关,提示Treg在慢性乙型肝炎中担负着重要的免疫调节作用,可能是造成乙肝病毒感染慢性化的重要因素。

Objective To evaluate the proportion of CD4 ＋ CDzs ＋ regulatory T cells （Tregs） in the irnmunopathogenesis of patients with chronic hepatitis B （CHB）, and to evaluate their poten- tial application in CHB immunotherapy. Methods Peripheral blood mononuclear cells （PBMCs） of 30 patients with CHB and 30 healthy donors were evaluated for the CD4 ＋ CD25 ＋ Treg phenotype and the proportion of CD4 ＋ CD25 ＋ Treg as a percentage of the total number of CD4 ＋ cells using flow cytometry, combined with the clinical condition of HBV infected patients of different peripheral blood CD4 ＋ CDzs ＋ Foxp3 ＋ regulatory T cells, and the ratio of the number of serum HBeAg and HB- VDNA content. Results Compared with the control group, HBV infections and peripheral blood CD4 ＋ CD25 ＋ Foxp3＋ regulatory T cells of HBV patients increased significantly [ （8.68% ± 1.23 % ） vs （1.38 %± 0.64 % ）, P 〈 0.01 ） ]. The peripheral blood CDa ＋ CD25 ＋ Foxp3 ＋ regulatory T cells of chronic hepatitis B carrier group was significantly different from that of the chronic hepatitis B re- covery group in the rate [ （8.68 %±1.23 % ） vs （2.63 % ± 1.38 % ）, P 〈 0.01） ]. HBVDNA viral load, HBeAg concentration and peripheral blood CD4 ＋ CD25 ＋ Foxp3 ＋ regulatory T cells had positive correlations （P〈0.01）. Conclusion HBV infection of peripheral blood CD4＋ CD25＋Foxp3＋ reg- ulatory T cells are significantly correlated with disease progression. Treg in patients with chronic hepatitis B carriers is significantly increased and associated with viral load, suggesting that Treg in patients with chronic hepatitis B plays an important immunoregulatory role, and may be an impor- tant cause for chronic hepatitis B virus infection.