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BACKGROUND/AIMS: T lymphocyte-mediated immune reactions are closely involved in the pathogenesis of HCV-induced chronic liver disease. Regulatory T cells are able to suppress HCV-specific T lymphocyte proliferation and cytokine secretion during chronic HCV infection. We wished to address to what extent regulatory T cells exist in the livers of HCV+ individuals, and what the role of such cells might be in disease progression. METHODS: We analysed the frequency and distribution of FOXP3+ cells, along with CD4, CD8 and CD20+ cells, in liver biopsies of 28 patients with chronic HCV and 14 patients with PBC, and correlated these data with histological parameters. RESULTS: A striking number of FOXP3+ cells were present in the portal tract infiltrates of HCV-infected livers. FOXP3+ cells were largely CD4+ and there was a remarkably consistent ratio of total CD4+:FOXP3+ cells in liver across a wide range of disease states of around 2:1. This differed substantially from the ratio observed in PBC (10:1, P=0.001). CONCLUSIONS: An unexpectedly high proportion of the cellular infiltrate in persistent HCV infection comprises FOXP3+ cells. The relative proportion of FOXP3+ cells remains similar in both mild and severe fibrosis. These cells are likely to play a critical role in intrahepatic immune regulation, although their overall role in disease progression remains to be determined.

Original publication

DOI

10.1016/j.jhep.2007.03.023

Type

Journal article

Journal

J Hepatol

Publication Date

09/2007

Volume

47

Pages

316 - 324

Keywords

Adult, B-Lymphocytes, Biopsy, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Disease Progression, Female, Forkhead Transcription Factors, Hepatitis C, Chronic, Humans, Leukocyte Count, Liver, Liver Cirrhosis, Biliary, Male, Middle Aged, Severity of Illness Index, T-Lymphocytes, Regulatory