title: Increased frequency of late-senescent T cells lacking CD127 in chronic hepatitis C disease.
abstract: BACKGROUND
  Hepatitis C virus (HCV) causes persistent disease in ~85% of infected individuals, where the viral replication appears to be tightly controlled by HCV-specific CD8+ T cells. Accumulation of senescent T cells during infection results in considerable loss of functional HCV-specific immune responses.
  
  
  METHODS
  We characterized the distinct T-cell phenotypes based on the expression of costimulatory molecules CD28 and CD27, senescence markers PD-1 and CD57, chronic immune activation markers CD38 and HLA-DR, and survival marker CD127 (IL-7R) by flow cytometry following activation of T cells using HCV peptides and phytohemagglutinin.
  
  
  RESULTS
  HCV-specific CD4+ and CD8+ T cells from chronic HCV (CHC) patients showed increased expression of PD-1. Furthermore, virus-specific CD4+ T cells of CHC-infected subjects displayed relatively increased expression of HLA-DR and CD38 relative to HCV-specific CD8+ T cells. The CD4+ and CD8+ T cells from HCV-infected individuals showed significant increase of late-differentiated T cells suggestive of immunosenescence. In addition, we found that the plasma viral loads positively correlated with the levels of CD57 and PD-1 expressed on T cells.
  
  
  CONCLUSIONS
  Chronic HCV infection results in increased turnover of late-senescent T cells that lack survival potentials, possibly contributing to viral persistence. Our findings challenge the prominence of senescent T-cell phenotypes in clinical hepatitis C infection.
authors.affiliation: Department of Medical Microbiology, Tropical Infectious Disease Research and Education Center (TIDREC), University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Muttiah
authors.initials: M
authors.lastname: Barathan
authors.forename: Rosmawati
authors.initials: R
authors.lastname: Mohamed
authors.forename: Alireza
authors.initials: A
authors.lastname: Saeidi
authors.forename: Jamuna
authors.initials: J
authors.lastname: Vadivelu
authors.forename: Li Y
authors.initials: LY
authors.lastname: Chang
authors.forename: Kaliappan
authors.initials: K
authors.lastname: Gopal
authors.forename: Mani R
authors.initials: MR
authors.lastname: Ram
authors.forename: Abdul W
authors.initials: AW
authors.lastname: Ansari
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Velu
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.forename: Esaki M
authors.initials: EM
authors.lastname: Shankar
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000328:Adult; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018959:CD57 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D055815:Young Adult
chemical_list: D018106:CD28 Antigens; D018959:CD57 Antigens; D006684:HLA-DR Antigens; D053699:Interleukin-7 Receptor alpha Subunit; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D051997:ADP-ribosyl Cyclase 1
keywords: CD38; CD57; HCV infection; IL-7R; PD-1; immunosenescence