慢性乙型肝炎患者血清转化生长因子β1与CD4^＋CD25^＋Foxp^3＋调节性T淋巴细胞的关系

Association between CD4^＋CD25^＋Foxp^3＋ regulatory T cells and serum transforming growth factor beta 1 in patients with chronic hepatitis B

目的调查慢性乙型肝炎患者转化生长因子β1（TGF β1）与CD4^＋CD25^＋Foxp^3＋调节性T淋巴细胞异常的关系。方法将实验对象分为慢性乙型肝炎（CHB）患者、无症状HBV携带者（AsC）、乙型肝炎恢复者、正常人对照4组。通过流式细胞术分析外周CD4^＋CD25^＋Foxp^3＋调节性T淋巴细胞的表型和频率以及实时荧光定量PCR分析Foxp3表达水平；并通过酶联免疫吸附法检测血清中TGF β1水平。根据数据不同采用方差分析或秩和检验进行统计学分析。结果CHB或AsC组外周CD4^＋T淋巴细胞中CD4^＋CD25^＋Foxp^3＋T淋巴细胞频率以及CD4^＋CD25^＋T淋巴细胞中Foxp3 mRNA表达水平显著高于正常人对照组，差异有统计学意义（P〈0．05）。CHB患者和AsC血清中TGF β1水平显著高于正常人和乙型肝炎恢复者，并与CD4^＋CD25^＋Foxp^3＋T淋巴细胞频率存在显著正相关（r=0．78，P〈0．01）。结论CHB和AsC患者TGF β1与CD4^＋CD25^＋Foxp^3＋调节性T淋巴细胞增高有密切关系。

Objective To investigate whether the CD4^＋CD25^＋Foxp^3＋ regulatory T cells are assocaited with serum TGF β 1 in patients with hepatitis B. Methods Patients with chronic hepatitis B （CHB）, chronic asypmtomatic carriers （AsC）, normal subjects （NS） and the resolved from HBV infection （Resolved） were recruited in this study. Flow cytometric analysis was used to detect the frequency and phenotype of peripheral CD4^＋CD25^＋Foxp^3＋ T cells, and Foxp3 gene expression were examined by real time PCR. Serum TGF β1 levels were measured by ELISA （enzyme-linked immunosorbent assay）. Results Patients with CHB or AsC exhibited significantly higher frequency of CD4^＋CD25^＋Foxp^3＋ T cells compared to healthy controls. CD4^＋CD25^＋ T ceils derived from patients with CHB and AsC expressed higher level of Foxp3-mRNA. Furthermore, the frequency of CD4^＋CD25^＋Foxp^3＋ regulatory T cells was correlated with serum HBV DNA copy numbers in patients with CHB and AsC. Our results indicated that the serum TGF β was increased in CHB and AsC patients compared to control patients, and that serum TGF β was correlated with the expression of Foxp3-mRNA and the frequency of CD4^＋CD25^＋Foxp^3＋ regulatory T cells in patients with CHB and AsC. Conclusions The findings have important implication in the understanding of the role and mechanism of aberrant CD4^＋CD25^＋Foxp^3＋ regulatory T cells in the maintenance of chronicity in hepatitis B patients.