慢性乙型肝炎患者肝组织内CD4^＋CD25^＋Foxp3^＋调节性细胞的作用

The role of liver-targeted CD4^＋ CD25^＋ Foxp3^＋ regulatory T cells in the patients with chronic hepatitis B

目的观察慢性乙型肝炎患者肝内调节性T细胞（Treg）与病情活动、肝细胞损伤的关系。方法对日本长崎大学医学院附属医齿学病院第一内科26例住院慢性乙型肝炎患者进行肝组织活检，采用免疫组织化学方法以单抗Foxp3、单抗CD3检测肝组织内Foxp3^＋细胞和CD3^＋细胞频率，计算Foxp3^＋／CD3^＋细胞比率，结合肝组织学炎症活动指数（HAI，采用Knodell评分系统）、ALT、AST、HBV DNA水平进行分析。数据用SPSS 13．0软件进行统计分析。结果Foxp3^＋Treg主要分布在门脉区；Foxp3^＋／CD3^＋细胞（％）在肝实质重度炎症组明显高于轻度炎症组（P=0．0076）；Foxp3^＋／CD3^＋细胞（％）的增高与血清ALT、AST水平呈正相关，相关系数分别0．438、0．436（P值分别为0．025、0．026），与血清HBV DNA水平有相关趋势，但差异无统计学意义。结论CD4^＋CD25^＋Foxp3^＋Treg在慢性乙型肝炎患者的发病机制中参与肝细胞的免疫损伤。

Objective To study the correlation between the percentage of intrahepatic regulatory T cell （Treg） and liver inflammatory activity in chronic hepatitis B （CHB） patients. Methods Twenty-six cases of CHB patients admitted to First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Nagasaki, Japan were enrolled and performed liver biopsy in this study. CD3^＋ cell and Foxp3^＋ cell in liver were detected by immunohistochemistry, the percentage of Foxp3^＋/CD3^＋ cell was determined. Clinical data including alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, hepatitis B virus （HBV） DNA level and the inflammatory activity of histological activity index score （HAl） of liver pathology using Knodell evaluating system were collected. The data was analyzed by SPSS 13.0 software. Results Foxp3^＋ Tregs in serial sections of CHB accumulated mainly in the portal area. There was a significance correlation between the percentage of Foxp3^＋/CD3^＋ cell and liver parenchyma inflammation （P = 0. 007 6）. Moreover, Foxp3^＋ Treg in CHB patients with high serum ALT or AST level presented in a higher frequency than in patients with low ALT or AST level. The difference between these two groups was statistically significant （rALT =0. 438, PALT = 0. 025 ; rAST =0. 436, PAST =0. 026）. There was a tendency between the percentage of Foxp3^＋/CD3^＋ cell in liver and HBV DNA level, however the correlation was not statistically significant. Conclusion It is suggested that CD4^＋ CD25^＋ Foxp3^＋ Treg may play a major role in the pathogenesis of liver injury in the CHB patients.