title: Increased hepatitis C virus (HCV)-specific CD4+CD25+ regulatory T lymphocytes and reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels.
abstract: CD4+CD25+ T regulatory cells may play a role in the different clinical presentations of chronic hepatitis C virus (HCV) infection by suppressing CD4+ T cell responses. Peripheral CD4+CD25+ T cells from chronic HCV carriers with normal and abnormal alanine aminotransferase (ALT) were analysed for specificity and effect on HCV-specific CD4+ T cell reactivity by flow cytometry for intracellular cytokine production and proliferation assay. HCV-specific CD4+CD25(+high) T cells consistently produced transforming growth factor (TGF)-beta but only limited amounts of interleukin (IL)-10 and no IL-2 and interferon (IFN)-gamma. The HCV-specific TGF-beta response by CD4+CD25(+high) T cells was significantly greater in patients with normal ALT compared to patients with elevated ALT. In addition, a significant inverse correlation was found between the HCV-specific TGF-beta response by CD4+CD25(+high) T cells and liver inflammation. In peripheral blood mononuclear cells (PBMC), both HCV antigen-induced IFN-gamma production and proliferation of CD4+ T cells were greater in patients with elevated ALT compared with patients with normal ALT. Depletion of CD4+CD25+ cells from PBMC resulted in an increase of both IFN-gamma production and proliferation of HCV-specific CD4+ T cells that was significantly greater in patients with normal ALT levels compared with patients with elevated ALT. In addition, CD4+CD25+ T cells from patients with normal ALT levels proved to be significantly more potent to suppress CD4+ T cell reactivity with respect to those from patients with elevated ALT. In conclusion, these data support the hypothesis that CD4+CD25+ cells may play a role in controlling chronic inflammatory response and hepatic damage in chronic HCV carriers.
authors.affiliation: Department of Public Health and Cellular Biology, University of Rome Tor Vergata, Via Montpellier 1, 00173 Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bolacchi
authors.forename: A
authors.initials: A
authors.lastname: Sinistro
authors.forename: C
authors.initials: C
authors.lastname: Ciaprini
authors.forename: F
authors.initials: F
authors.lastname: Demin
authors.forename: M
authors.initials: M
authors.lastname: Capozzi
authors.forename: F C
authors.initials: FC
authors.lastname: Carducci
authors.forename: C M J
authors.initials: CM
authors.lastname: Drapeau
authors.forename: G
authors.initials: G
authors.lastname: Rocchi
authors.forename: A
authors.initials: A
authors.lastname: Bergamini
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D015703:Antigens, CD / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma; D000410:Alanine Transaminase