title: Evaluation of circulating CD4+CD25+ and liver-infiltrating Foxp3+ cells in HCV-associated liver disease.
abstract: In hepatitis C virus (HCV)-associated liver disease, the immune system is unable to clear the viral infection. Previous studies have raised the possibility of an involvement of regulatory T cells (Tregs). In this study, we analysed the peripheral blood from 30 patients with HCV-associated chronic liver disease and 20 healthy controls by flow cytometry for the evaluation of the Treg population [CD4⁺CD25hi forkhead box protein 3 (Foxp3)⁺], as well as the activated/effector CD4⁺ T cells (CD4⁺CD25low) and IFN-γ-secreting cells. We also analysed liver biopsies of the patients by immunohistochemical evaluation of Foxp3⁺ cells. Our results showed higher proportions of CD4⁺CD25low and IFN-γ⁺ cells in the patients than in the controls. By contrast, the proportions of peripheral CD4⁺CD25hi cells did not significantly differ. The 11 patients displaying Foxp3⁺ cells in the liver infiltrates showed significantly higher proportions of peripheral CD4⁺CD25low cells. Moreover, we found lower serum transaminase levels in the patients than in the controls, as shown by Foxp3⁺ immunohistochemistry, although these results were only statistically significant as regards alanine transaminase (ALT). In conclusion, these data suggest that the presence of Tregs infiltrating the liver is associated with high levels of activated/effector T cells in the peripheral blood and lower activity of hepatitis. Therefore, liver-infiltrating Tregs may play a role in limiting tissue damage and may thus support an effective immune response against HCV.
authors.affiliation: Interdisciplinary Research Center of Autoimmune Diseases and Department of Medical Sciences, University A. Avogadro of Eastern Piedmont, 28100 Novara, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Amoroso
authors.forename: Fabio
authors.initials: F
authors.lastname: D'Amico
authors.forename: Maria
authors.initials: M
authors.lastname: Consolo
authors.forename: Evangelia
authors.initials: E
authors.lastname: Skarmoutsou
authors.forename: Sergio
authors.initials: S
authors.lastname: Neri
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
authors.forename: Maria Clorinda
authors.initials: MC
authors.lastname: Mazzarino
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015704:CD4 Antigens / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D015759:Ionomycin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000821:virology; D008107:Liver Diseases / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D015759:Ionomycin; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D013755:Tetradecanoylphorbol Acetate