Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, 's-Gravendijkwal 230, Rotterdam, The Netherlands.
J Hepatol. 2010 Mar;52(3):315-21. doi: 10.1016/j.jhep.2009.12.013. Epub 2009 Dec 24.
BACKGROUND & AIMS: Weak hepatitis C virus (HCV) specific immunity in peripheral blood has been shown to be partially controlled by regulatory T cells (Treg). However, little is known about Treg present in livers of HCV-infected patients, their association with clinical parameters, and immunopathology resulting in disease progression.
The frequency and phenotype of CD4+FoxP3+ Treg, conventional CD4+ T cells, and the distribution of lymphocytes and leukocytes were studied by multi-color flowcytometry in liver and peripheral blood of 43 chronic HCV patients at different phases of liver disease. Comparisons between healthy blood and liver and correlations with disease parameters were made.
An extensive lymphocyte infiltration containing abundant numbers of CD4+FoxP3+ Treg was present in HCV-infected livers, while absent from healthy liver. Moreover, in all patients, intrahepatic CD4+FoxP3+ Treg showed a fully differentiated and highly activated phenotype on the basis of the surface markers CD45RO, CCR7, CTLA-4 and HLA-DR. These Treg were more numerous in those HCV-infected livers showing only limited fibrosis. However, HCV RNA loads or alanine transaminase levels did not correlate with CD4+FoxP3+ Treg frequencies.
Our data demonstrate that large numbers of highly activated and differentiated CD4+FoxP3+ Treg localize to the infiltrated chronic HCV-infected liver and may result in limiting the extent of fibrosis. This suggests that CD4+FoxP3+ Treg play a pivotal role in limiting collateral damage by suppressing excessive HCV-induced immune activation.
外周血中较弱的丙型肝炎病毒（HCV）特异性免疫已被证明部分受调节性 T 细胞（Treg）控制。然而，人们对 HCV 感染患者肝脏中存在的 Treg、它们与临床参数的关系以及导致疾病进展的免疫病理学知之甚少。
通过多色流式细胞术研究了 43 例不同阶段 HCV 感染患者肝和外周血中 CD4+FoxP3+Treg、常规 CD4+T 细胞的频率和表型以及淋巴细胞和白细胞的分布，并与健康血液和肝脏进行了比较，并与疾病参数进行了相关性分析。
在 HCV 感染的肝脏中存在广泛的淋巴细胞浸润，其中含有大量的 CD4+FoxP3+Treg，而在健康肝脏中则不存在。此外，在所有患者中，基于 CD45RO、CCR7、CTLA-4 和 HLA-DR 等表面标志物，肝内 CD4+FoxP3+Treg 表现出完全分化和高度活化的表型。在仅表现出有限纤维化的 HCV 感染肝脏中，这些 Treg 数量更多。然而，HCV RNA 载量或丙氨酸氨基转移酶水平与 CD4+FoxP3+Treg 频率无关。
我们的数据表明，大量高度活化和分化的 CD4+FoxP3+Treg 定位于浸润性慢性 HCV 感染的肝脏，可能导致纤维化程度受限。这表明 CD4+FoxP3+Treg 通过抑制过度的 HCV 诱导的免疫激活在限制继发损伤方面发挥关键作用。
