title: Hepatitis C virus induces regulatory T cells by naturally occurring viral variants to suppress T cell responses.
abstract: Regulatory T cell markers are increased in chronically infected individuals with the hepatitis C virus (HCV), but to date, the induction and maintenance of Tregs in HCV infection has not been clearly defined. In this paper, we demonstrate that naturally occurring viral variants suppress T cell responses to cognate NS3(358-375) in an antigen-specific manner. Of four archetypal variants, S370P induced regulatory T cell markers in comparison to NS3(358-375)-stimulated CD4 T cells. Further, the addition of variant-specific CD4 T cells back into a polyclonal culture in a dose-dependent manner inhibited the T cell response. These results suggest that HCV is able to induce antigen-specific regulatory T cells to suppress the antiviral T cell response in an antigen-specific manner, thus contributing to a niche within the host that could be conducive to HCV persistence.
authors.affiliation: Division of Histocompatibility and Immunogenetics, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Cusick
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Schiller
authors.forename: Joan C
authors.initials: JC
authors.lastname: Gill
authors.forename: David D
authors.initials: DD
authors.lastname: Eckels
mesh_terms: D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D057131:Immune Evasion; D008213:Lymphocyte Activation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D017735:Virus Latency; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; D006680:HLA Antigens; D017361:Viral Nonstructural Proteins; C418974:FOXP3 protein, human; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases