title: Cellular immune responses associated with occult hepatitis C virus infection of the liver.
abstract: Occult hepatitis C virus (HCV) infection is a type of recently identified chronic infection that is evidenced only by detection of HCV RNA in liver; patients consistently test negative for antibodies to HCV and HCV RNA in serum. Using ex vivo and in vitro measures of T-cell responses, we have identified functional virus-specific memory CD4(+) and CD8(+) T cells in the peripheral blood of patients with occult HCV infection. The features of the virus-specific T cells were consistent with immune surveillance functions, supporting previous exposure to HCV. In addition, the magnitudes of CD4(+) and CD8(+) T-cell responses were in parallel and correlated inversely with the extent of liver HCV infection. The detection of HCV-specific T cells in individuals in whom HCV RNA can persist in the liver despite the absence of viremia and antibodies indicates that HCV replication is prolonged in the face of virus-specific CD4(+) and CD8(+) T-cell responses. These findings demonstrate that HCV-specific cellular immune responses are markers not only of previous exposure to and recovery from HCV but also of ongoing occult HCV infection.
authors.affiliation: Fundación para el Estudio de las Hepatitis Virales, Guzmán el Bueno, 72, 28015 Madrid, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Quiroga
authors.forename: Silvia
authors.initials: S
authors.lastname: Llorente
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Castillo
authors.forename: Elena
authors.initials: E
authors.lastname: Rodríguez-Iñigo
authors.forename: Margarita
authors.initials: M
authors.lastname: Pardo
authors.forename: Vicente
authors.initials: V
authors.lastname: Carreño
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D019041:L-Selectin / Q000032:analysis; D037181:Lectins, C-Type; D008099:Liver / Q000821:virology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D019041:L-Selectin; D037181:Lectins, C-Type; D012367:RNA, Viral; D000099192:CD69 Antigens