title: Divergent contributions of regulatory T cells to the pathogenesis of chronic hepatitis C.
abstract: Hepatitis C virus, a small single-stranded RNA virus, is a major cause of chronic liver disease. Resolution of primary hepatitis C virus infections depends upon the vigorous responses of CD4(+) and CD8(+) T cells to multiple viral epitopes. Although such broad CD4(+) and CD8(+) T-cell responses are readily detected early during the course of infection regardless of clinical outcome, they are not maintained in individuals who develop chronic disease. Purportedly, a variety of factors contribute to the diminished T-cell responses observed in chronic, virus-infected patients including the induction of and biological suppression by CD4(+)FoxP3(+) regulatory T cells. Indeed, a wealth of evidence suggests that regulatory T cells play diverse roles in the pathogenesis of chronic hepatitis C, impairing the effector T-cell response and viral clearance early during the course of infection and suppressing liver injury as the disease progresses. The factors that affect the generation and biological response of regulatory T cells in chronic, hepatitis C virus-infected patients is discussed.
authors.affiliation: Department of Medicine; Rhode Island Hospital and the Warren Alpert Medical School of Brown University; Providence, RI USA.
authors.forename: Ayssa A
authors.initials: AA
authors.lastname: Self
authors.forename: Phyllis T
authors.initials: PT
authors.lastname: Losikoff
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gregory
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: dendritic cells; hepatitis C; immune tolerance; liver disease; regulatory T cells