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Expansion of CD4 + CD25 + FoxP3 + regulatory T cells in hepatitis C virus‐related chronic hepatitis, cirrhosis and hepatocellular carcinoma
Author(s) -
Yoshizawa Kai,
Abe Hiroshi,
Kubo Yasuhito,
Kitahara Takuya,
Aizawa Ryoichi,
Matsuoka Mika,
Aizawa Yoshio
Publication year - 2010
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2009.00587.x
Subject(s) - hepatocellular carcinoma , foxp3 , cirrhosis , medicine , il 2 receptor , hepatitis c virus , population , immunology , hepatitis c , liver disease , virus , t cell , immune system , environmental health
Aim: 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. Methods: 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. Results: 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. Conclusion: 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.