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Hepatol Res. 2010 Feb;40(2):179-87. doi: 10.1111/j.1872-034X.2009.00587.x. Epub 2010 Jan 11.

Expansion of CD4(+)CD25(+)FoxP3(+) regulatory T cells in hepatitis C virus-related chronic hepatitis, cirrhosis and hepatocellular carcinoma.

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Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine Aoto Hospital, Katsushika-ku, Tokyo, Japan.



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.

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