title: Increased expression of regulatory Tr1 cells in recurrent hepatitis C after liver transplantation.
abstract: Immune response failure during HCV infection has been associated with the activity of regulatory T cells. Hepatitis C-related cirrhosis is the main reason for liver transplantation. However, 80% of transplanted patients present an accelerated recurrence of the disease. This study assessed the involvement of regulatory T-cell subsets (CD4+CD25+ cells: 'Treg' and CD49b+CD18+ cells: 'T regulatory-1' cells), in the recurrence of HCV after liver transplantation, using transcriptomic analysis, ELISA assays on serum samples and immunohistochemistry on liver biopsies from liver recipients 1 and 5 years after transplantation. Three groups of patients were included: stable HCV-negative recipients and those with mild and severe hepatitis C recurrence. At 5 years, Treg markers were overexpressed in all HCV+ recipients. By contrast, Tr1 markers were only overexpressed in patients with severe recurrence. At 1 year, a trend toward the overexpression of Tr1 was noted in patients evolving toward severe recurrence. IL-10 production, a characteristic of the Tr1 subset, was enhanced in severe recurrence at both 1 and 5 years. These results suggest that Tr1 are enhanced during severe HCV recurrence after liver transplantation and could be predictive of HCV recurrence. High levels of IL-10 at 1 year could be predictive of severe recurrence, and high IL-10 producers might warrant more intensive management.
authors.affiliation: Laboratoire de Biologie Cellulaire, Université René Descartes, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Carpentier
authors.forename: F
authors.initials: F
authors.lastname: Conti
authors.forename: F
authors.initials: F
authors.lastname: Stenard
authors.forename: L
authors.initials: L
authors.lastname: Aoudjehane
authors.forename: C
authors.initials: C
authors.lastname: Miroux
authors.forename: P
authors.initials: P
authors.lastname: Podevin
authors.forename: O
authors.initials: O
authors.lastname: Morales
authors.forename: S
authors.initials: S
authors.lastname: Chouzenoux
authors.forename: O
authors.initials: O
authors.lastname: Scatton
authors.forename: H
authors.initials: H
authors.lastname: Groux
authors.forename: C
authors.initials: C
authors.lastname: Auriault
authors.forename: Y
authors.initials: Y
authors.lastname: Calmus
authors.forename: V
authors.initials: V
authors.lastname: Pancre
authors.forename: N
authors.initials: N
authors.lastname: Delhem
mesh_terms: D000328:Adult; D018821:CD18 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015967:Gene Expression Regulation, Viral; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D039421:Integrin alpha2 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018821:CD18 Antigens; D039421:Integrin alpha2; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10