title: Immunological changes in different patient populations with chronic hepatitis C virus infection.
abstract: OBJECTIVE
  To investigate killer inhibitory and activating receptor expression by natural killer (NK), natural killer T-like (NKT-like) and CD8+ T lymphocytes in patients with chronic hepatitis C virus (HCV) infection with elevated and with persistently normal alanine aminotransferase (PNALT).
  
  
  METHODS
  The percentage of peripheral blood Treg cells, KIR2DL3, ILT-2, KIR3DL1, CD160, NKG2D, NKG2C expressing NK, T and NKT-like cells, cytokine production and NK cytotoxicity were determined by flow cytometry. Twenty-one patients with chronic HCV infection with elevated alanine aminotransferase, 11 HCV carriers with persistently normal alanine aminotransferase and 15 healthy volunteers were enrolled.
  
  
  RESULTS
  No significant differences were observed in the percentage of total T, NK or NKT-like cells between study groups. Comparing the activating and inhibitory receptor expression by NK cells obtained from HCV carriers with PNALT and chronic HCV hepatitis patients with elevated alanine aminotransferase, NKG2D activating receptor expression was the only receptor showing a significant difference. NKG2D expression of NK cells was significantly lower in patients with elevated alanine aminotransferase. The expression of CD160, NKG2D and NKG2C activating receptor by CD8+ T cells were significantly lower in patients with chronic HCV hepatitis than in healthy controls and in HCV carriers with PNALT. Plasma TGF-β1 levels inversely correlated with NKG2D expression by NK cells. In vitroTGF-β1 treatment inhibited NK cells cytotoxic activity and downregulated NKG2D expression. CD8+ T cells from HCV carriers with PNALT showed significantly elevated expression of CD160, NKG2D and NKG2C activating receptors compared to chronic HCV patients with elevated alanine aminotransferase. Enhanced expression of inhibitory KIR2DL3 receptor, and decreased ILT-2 expression on NK cells were also found in chronic hepatitis C patients compared to healthy controls.
  
  
  CONCLUSIONS
  Our study demonstrated a complex dysregulation of activating and inhibitory receptor expression, such as decreased NKG2D and CD160 activating receptor expression and increased KIR2DL3 inhibitory receptor expression by NK and cytotoxic T cells and may provide further mechanism contributing to defective cellular immune functions in chronic hepatitis C. Increased NKG2D receptor expression in HCV patients with persistently normal ALT suggests an important pathway for sustaining NK and CD8 T cell function and a protective role against disease progression.
authors.affiliation: Laszlo Szereday, Matyas Meggyes, Melinda Halasz, Julia Szekeres-Bartho, Department of Medical Microbiology and Immunology, University of Pecs, Clinical Centre, 7624 Pecs, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Szereday
authors.affiliation: Laszlo Szereday, Matyas Meggyes, Melinda Halasz, Julia Szekeres-Bartho, Department of Medical Microbiology and Immunology, University of Pecs, Clinical Centre, 7624 Pecs, Hungary.
authors.forename: Matyas
authors.initials: M
authors.lastname: Meggyes
authors.affiliation: Laszlo Szereday, Matyas Meggyes, Melinda Halasz, Julia Szekeres-Bartho, Department of Medical Microbiology and Immunology, University of Pecs, Clinical Centre, 7624 Pecs, Hungary.
authors.forename: Melinda
authors.initials: M
authors.lastname: Halasz
authors.affiliation: Laszlo Szereday, Matyas Meggyes, Melinda Halasz, Julia Szekeres-Bartho, Department of Medical Microbiology and Immunology, University of Pecs, Clinical Centre, 7624 Pecs, Hungary.
authors.forename: Julia
authors.initials: J
authors.lastname: Szekeres-Bartho
authors.affiliation: Laszlo Szereday, Matyas Meggyes, Melinda Halasz, Julia Szekeres-Bartho, Department of Medical Microbiology and Immunology, University of Pecs, Clinical Centre, 7624 Pecs, Hungary.
authors.forename: Alajos
authors.initials: A
authors.lastname: Par
authors.affiliation: Laszlo Szereday, Matyas Meggyes, Melinda Halasz, Julia Szekeres-Bartho, Department of Medical Microbiology and Immunology, University of Pecs, Clinical Centre, 7624 Pecs, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Par
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D003602:Cytotoxicity, Immunologic; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000821:virology; D010641:Phenotype; D011379:Prognosis; D011971:Receptors, Immunologic / Q000097:blood; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D016207:Cytokines; D011971:Receptors, Immunologic; D000410:Alanine Transaminase
keywords: Cytokine; Cytotoxicity; Hepatitis C; NKG2D; Natural killer cell