title: Reduced frequencies of NKp30+NKp46+, CD161+, and NKG2D+ NK cells in acute HCV infection may predict viral clearance.
abstract: OBJECTIVE
  While the majority of HCV-infected patients progress to chronic hepatitis, a small fraction of individuals are able to clear the virus. Resolution of infection occurs within the first few weeks to months of infection, suggesting that innate immune functions may be critical for early control. Epidemiologic data support a role for particular NK cell receptor bearing populations in this control, yet the mechanism by which NK cells respond to HCV early in infection is unknown.
  
  
  METHODS
  Changes in the phenotype and function of NK cells were investigated in a cohort of 43 individuals identified during various stages of HCV infection with different clinical outcomes.
  
  
  RESULTS
  Acute, chronic, and resolved HCV infections were characterized by an expansion of CD56(neg) NK cells. Furthermore, increased levels of HLA-C-binding KIR(+) NK cells were observed in HCV resolvers, while all stages of HCV infection were associated with reduced percentages of NKG2D(+), NKp30(+), and NKp46(+) NK cells, and a slight increase in the ability of NK cells to respond to target cells bearing the ligands for these receptors. In contrast, NKG2A(+) and CD94(+) NK cells were elevated in acute and chronic HCV infection, but not in resolved infection. Most importantly, in acute infection, lower frequencies of NKp30(+), NKp46(+), CD161(+), and NKG2D(+) NK cells were observed in patients who were subsequently able to clear HCV infection than in those becoming chronically infected.
  
  
  CONCLUSIONS
  These data implicate particular populations of NK cells in the early control and clearance of HCV infection.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA. galter@partners.org
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jost
authors.forename: Suzannah
authors.initials: S
authors.lastname: Rihn
authors.forename: Laura L
authors.initials: LL
authors.lastname: Reyor
authors.forename: Brian E
authors.initials: BE
authors.lastname: Nolan
authors.forename: Musie
authors.initials: M
authors.lastname: Ghebremichael
authors.forename: Ronald
authors.initials: R
authors.lastname: Bosch
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Georg M
authors.initials: GM
authors.lastname: Lauer
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D015236:HLA-C Antigens / Q000378:metabolism; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000145:classification* / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000378:metabolism; D054340:Receptors, KIR / Q000378:metabolism; D019562:Viral Load / Q000276:immunology; D055815:Young Adult
chemical_list: D015236:HLA-C Antigens; C527203:KLRB1 protein, human; C527085:KLRK1 protein, human; D037181:Lectins, C-Type; C112260:NCR1 protein, human; C431710:NCR3 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D054340:Receptors, KIR