title: Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis.
abstract: The mechanisms that lead to loss of tolerance in autoimmune disease have remained both elusive and diverse, including both genetic predisposition and generic dysregulation of critical mononuclear cell subsets. In primary biliary cirrhosis (PBC), patients exhibit a multilineage response to the E2 component of pyruvate dehydrogenase involving antibody as well as autoreactive CD4 and CD8 responses. Recent data from murine models of PBC have suggested that a critical mechanism of biliary destruction is mediated by liver-infiltrating CD8 cells. Further, the number of autoreactive liver-infiltrating CD4 and CD8 cells is significantly higher in liver than blood in patients with PBC. Based on this data, we have studied the frequencies and phenotypic characterization of both CD4 and CD8 regulatory T cell components in both patients with PBC and age-sex matched controls. Our data is striking and indicate that CD8 Treg populations from PBC patients, but not controls, have significant phenotypic alterations, including increased expression of CD127 and reduced CD39. Furthermore, in vitro induction of CD8 Tregs by incubation with IL10 is significantly reduced in PBC patients. Importantly, the frequencies of circulating CD4+CD25+ and CD8+ and CD28- T cell subpopulations are not significantly different between patients and controls. In conclusion, these data identify the CD8 Treg subset as a regulatory T cell subpopulation altered in patients with PBC.
authors.affiliation: Division of Internal Medicine and Hepatobiliary, Immunopathology Unit, IRCCS Istituto Clinico Humanitas, Rozzano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bernuzzi
authors.forename: Daniela
authors.initials: D
authors.lastname: Fenoglio
authors.forename: Florinda
authors.initials: F
authors.lastname: Battaglia
authors.forename: Marco
authors.initials: M
authors.lastname: Fravega
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Francesco
authors.initials: F
authors.lastname: Indiveri
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Mauro
authors.initials: M
authors.lastname: Podda
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.forename: Gilberto
authors.initials: G
authors.lastname: Filaci
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D001081:Apyrase / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002465:Cell Movement; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D053699:Interleukin-7 Receptor alpha Subunit; D016753:Interleukin-10; D001081:Apyrase; C067869:CD39 antigen