title: Cellular immune responses in seronegative sexual contacts of acute hepatitis C patients.
abstract: Acute hepatitis C virus (HCV) is typically defined as new viremia and antibody seroconversion. Rates and immunologic correlates of hepatitis C clearance have therefore been based on clearance of viremia only in individuals who initially had an antibody response. We sought to characterize the immunological correlates of clearance in patients with acute hepatitis C and their sexual contacts. We prospectively determined CD4(+) and CD8(+) cytotoxic T-lymphocyte responses in index patients with acute HCV and their sexual contacts who developed acute infection, either with or without spontaneous clearance, as well as those contacts who never developed viremia. Responses were measured using proliferation and ELISpot assays for CD4(+) and CD8(+) responses. We demonstrate in this prospective study that cellular immune responses can develop in exposed but persistently aviremic and antibody-negative individuals as well as those individuals with spontaneous clearance of acute HCV. These findings lend further credence to the importance of cellular immune responses in recovery from HCV and suggest that low exposure to HCV may lead to development of HCV-specific immune responses without ongoing HCV replication. This finding has important implications for HCV vaccine and therapeutic development.
authors.affiliation: Department of Infectious Diseases, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115, USA. Sanaa.Kamal@link.net
authors.forename: Sanaa M
authors.initials: SM
authors.lastname: Kamal
authors.forename: Ashraf
authors.initials: A
authors.lastname: Amin
authors.forename: Mohamed
authors.initials: M
authors.lastname: Madwar
authors.forename: Camilla S
authors.initials: CS
authors.lastname: Graham
authors.forename: Qi
authors.initials: Q
authors.lastname: He
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al Tawil
authors.forename: Jens
authors.initials: J
authors.lastname: Rasenack
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Nakano
authors.forename: Betty
authors.initials: B
authors.lastname: Robertson
authors.forename: Alaa
authors.initials: A
authors.lastname: Ismail
authors.forename: Margaret James
authors.initials: MJ
authors.lastname: Koziel
mesh_terms: D000208:Acute Disease; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006526:Hepatitis C / Q000276:immunology* / Q000635:transmission; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D012725:Sexual Behavior; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018937:Hepatitis C Antibodies; D007371:Interferon-gamma