title: CD161 expression on hepatitis C virus-specific CD8+ T cells suggests a distinct pathway of T cell differentiation.
abstract: Hepatitis C virus (HCV) causes chronic infection accompanied by a high risk of liver failure and hepatocellular carcinoma. CD8+ T cell responses are important in the control of viremia. However, the T cell response in chronic infection is weak both in absolute numbers and in the range of epitopes targeted. In order to explore the biology of this response further, we analyzed expression of a panel of natural killer cell markers in HCV compared with other virus-specific T cell populations as defined by major histocompatibility complex class I tetramers. We found that CD161 was significantly expressed on HCV-specific cells (median 16.8%) but not on CD8+ T cells specific for human immunodeficiency virus (3.3%), cytomegalovirus (3.4%), or influenza (3.4%). Expression was seen in acute, chronic, and resolved disease and was greatest on intrahepatic HCV-specific T cells (median 57.6%; P < 0.05). Expression of CD161 was also found on hepatitis B virus-specific CD8+ T cells. In general, CD161+CD8+ T cells were found to be CCR7- "effector memory" T cells that could produce proinflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) but contained scanty amounts of cytolytic molecules (granzyme B and perforin) and proliferated poorly in vitro. Expression of CD161 on CD8+ T cells was tightly linked to that of CXCR6, a chemokine with a major role in liver homing.
  
  
  CONCLUSIONS
  We propose that expression of CD161 indicates a unique pattern of T cell differentiation that might help elucidate the mechanisms of HCV immunity and pathogenesis.
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: John W
authors.initials: JW
authors.lastname: Northfield
authors.forename: Victoria
authors.initials: V
authors.lastname: Kasprowicz
authors.forename: Michaela
authors.initials: M
authors.lastname: Lucas
authors.forename: Nadine
authors.initials: N
authors.lastname: Kersting
authors.forename: Bertram
authors.initials: B
authors.lastname: Bengsch
authors.forename: Bertram
authors.initials: B
authors.lastname: Bengsh
authors.forename: Arthur
authors.initials: A
authors.lastname: Kim
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Phillips
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.forename: Georg
authors.initials: G
authors.lastname: Lauer
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000208:Acute Disease; D000954:Antigens, Surface / Q000235:genetics*; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002454:Cell Differentiation; D002455:Cell Division; D003587:Cytomegalovirus / Q000276:immunology; D006678:HIV / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology* / Q000472:pathogenicity; D006509:Hepatitis B / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D037181:Lectins, C-Type / Q000235:genetics*; D055651:NK Cell Lectin-Like Receptor Subfamily B; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology
chemical_list: D000954:Antigens, Surface; D017252:CD3 Complex; C527203:KLRB1 protein, human; D019394:Ki-67 Antigen; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B