%0 Journal Article
%T Overexpression of Regulatory T Cells Type 1 (Tr1) Specific Markers in a Patient with HCV-Induced Hepatocellular Carcinoma
%A Laurissa Ouaguia
%A Olivier Morales
%A Dhafer Mrizak
%A Khaldoun Ghazal
%A Emmanuel Boleslawski
%A Claude Auriault
%A V¨¦ronique Pancr¨¦
%A Yvan de Launoit
%A Filom¨¦na Conti
%A Nadira Delhem
%J ISRN Hepatology
%D 2013
%R 10.1155/2013/928485
%X Hepatitis C virus (HCV) is an important causative agent of liver disease, but factors that determine the resolution or progression of infection are poorly understood. In this study, we suggested that existence of immunosuppressive mechanisms, supported by regulatory T cells and especially the regulatory T cell 1 subset (Tr1), may explain the impaired immune response during infection and thus the fibrosis aggravation to hepatocellular carcinoma (HCC). Using quantitative real-time PCR, we investigated the intra-hepatic presence of Tr1 cells in biopsies from a genotype 1b infected patient followed for an 18-year period from cirrhosis to HCC. We described a significant increase of gene expression in particular for the cytokines IL-10, TGF-¦Â, and their receptors that were perfectly correlated with an increased expression of the Tr1 specific markers (combined expression of CD4, CD18, and CD49b). This was strongly marked since the patient evolved in the pathology and could explain the failure of the treatment. In conclusion, evidence of regulatory T cell installation in the liver of chronically infected patient with cirrhosis and HCC suggests for the first time a key role for these cells in the course of HCV infection. 1. Introduction Hepatitis C virus (HCV) is a parentally transmitted hepatotropic RNA virus that causes chronic hepatitis, which may lead to cirrhosis and hepatocellular carcinoma (HCC) [1]. Evidence suggests that clearance and control of HCV infection during acute phase is dependent on vigorous and multispecific CD4 and CD8 T lymphocyte responses [2, 3]. On the contrary, the development and maintenance of chronic infection is linked to weak or absence of HCV-specific Th1 response and to the presence of Th2 cytokines (IL-4 and IL-10) [4, 5]. So, some studies have implicated IL-10 in HCV pathogenesis [4, 6]. Regulatory T cell 1 (Tr1) was first described in 1996 [7, 8] as a further subtype of CD4 T cells, without specific markers but with cytokine profile distinct from that of Th1 or Th2 cells. Indeed, they were shown as secreting high level of IL-10, moderate levels of IFN-¦Ã and IL-5, quite undetectable IL-4, and low amounts of transforming growth factor (TGF-¦Â). Recent studies have suggested that Tr1 could be induced against bacterial, viral and parasite antigens in vivo and might prevent infection-induced immunopathology or prolong pathogen persistence by suppressing protective Th1 response [9, 10] but has never been directly implicated in hepatitis C viral pathogenesis. The dysfunction of the immune response against HCV could be explained by
%U http://www.hindawi.com/journals/isrn.hepatology/2013/928485/