Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine Aoto Hospital, Katsushika-ku, Tokyo, Japan.
Hepatol Res. 2010 Feb;40(2):179-87. doi: 10.1111/j.1872-034X.2009.00587.x. Epub 2010 Jan 11.
Regulatory T (Treg) cells may play a pivotal role in the persistence of hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). Therefore, we examined their frequency in peripheral blood from patients with HCV-positive chronic hepatitis (CH), cirrhosis (LC) and HCC.
Treg cells were identified as CD4(+), CD25(+) and FoxP3(+) T lymphocytes using three-color FACS. The frequency of Treg cells was expressed as a percentage of the total CD4(+) T lymphocytes, and the phenotype of Treg cells was examined using CD45RA.
Treg cells were significantly increased in CH (5.88 +/- 0.19%, n = 76; P < 0.01), LC (6.10 +/- 0.28%, n = 40; P < 0.001) and HCC (6.80 +/- 0.30%, n = 57; P < 0.0001) compared to healthy control (5.13 +/- 0.25%, n = 31). However, Treg cells were not increased with the progression of fibrosis or the grade of inflammations. Treg cells were slightly increased in early-stage HCC (6.91 +/- 0.40%) compared with advanced-stage HCC (6.58 +/- 0.39%), but these results were not statistically significant. In a serial examination, a distinct increase in Treg cells after local therapy for early-stage HCC was a hallmark of early recurrence. Most expanded Treg cells in HCC were CD45RA(-), suggesting that a memory-type Treg population had differentiated in the periphery and not in the thymus.
We observed an increase in Treg cells in HCV-related chronic liver disease, particularly in HCC, and these cells were shown to be memory-type Treg cells.
调节性 T（Treg）细胞可能在丙型肝炎病毒（HCV）感染的持续存在和肝细胞癌（HCC）的发展中起关键作用。因此，我们检查了外周血中丙型肝炎阳性慢性肝炎（CH）、肝硬化（LC）和 HCC 患者的 Treg 细胞频率。
使用三色 FACS 鉴定 Treg 细胞为 CD4(+)、CD25(+)和 FoxP3(+)T 淋巴细胞。Treg 细胞的频率以总 CD4(+)T 淋巴细胞的百分比表示，并使用 CD45RA 检查 Treg 细胞的表型。
与健康对照组（5.13 +/- 0.25%，n = 31）相比，CH（5.88 +/- 0.19%，n = 76；P < 0.01）、LC（6.10 +/- 0.28%，n = 40；P < 0.001）和 HCC（6.80 +/- 0.30%，n = 57；P < 0.0001）中 Treg 细胞显著增加。然而，Treg 细胞的增加与纤维化的进展或炎症的程度无关。与晚期 HCC（6.58 +/- 0.39%）相比，早期 HCC（6.91 +/- 0.40%）中 Treg 细胞略有增加，但这些结果无统计学意义。在连续检查中，早期 HCC 局部治疗后 Treg 细胞的明显增加是早期复发的标志。HCC 中扩增的大多数 Treg 细胞为 CD45RA(-)，提示外周分化的是记忆型 Treg 细胞，而不是胸腺分化的 Treg 细胞。
我们观察到丙型肝炎相关慢性肝病，尤其是 HCC 中 Treg 细胞增加，这些细胞为记忆型 Treg 细胞。
