title: Overexpression of Regulatory T Cells Type 1 (Tr1) Specific Markers in a Patient with HCV-Induced Hepatocellular Carcinoma.
abstract: 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-β, 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.
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, 1 rue du Professeur Calmette, 59021 Lille Cedex, France.
authors.forename: Laurissa
authors.identifier: 0000-0002-3216-3950
authors.initials: L
authors.lastname: Ouaguia
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, 1 rue du Professeur Calmette, 59021 Lille Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Morales
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, 1 rue du Professeur Calmette, 59021 Lille Cedex, France.
authors.forename: Dhafer
authors.identifier: 0000-0003-1767-3300
authors.initials: D
authors.lastname: Mrizak
authors.affiliation: UPMC Université Paris 6, Inserm, UMR-S938, Centre de Recherche Saint Antoine, 75012 Paris, France.
authors.forename: Khaldoun
authors.identifier: 0000-0002-3006-9274
authors.initials: K
authors.lastname: Ghazal
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, 1 rue du Professeur Calmette, 59021 Lille Cedex, France; Service de Chirurgie Digestive et Transplantations, Hôpital Huriez, CHU, Université Nord-de-France, 59000 Lille, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Boleslawski
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, 1 rue du Professeur Calmette, 59021 Lille Cedex, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Auriault
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, 1 rue du Professeur Calmette, 59021 Lille Cedex, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Pancré
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, 1 rue du Professeur Calmette, 59021 Lille Cedex, France.
authors.forename: Yvan
authors.initials: Y
authors.lastname: de Launoit
authors.affiliation: UPMC Université Paris 6, Inserm, UMR-S938, Centre de Recherche Saint Antoine, 75012 Paris, France; Centre de Transplantation Hépatique, Pôle Digestif, APHP, Hôpital Saint Antoine, 184 rue de Faubourg Saint Antoine, 75012 Paris, France.
authors.forename: Filoména
authors.initials: F
authors.lastname: Conti
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, 1 rue du Professeur Calmette, 59021 Lille Cedex, France.
authors.forename: Nadira
authors.identifier: 0000-0001-5335-4222
authors.initials: N
authors.lastname: Delhem