title: Peripheral loss of CD8(+) CD161(++) TCRVα7·2(+) mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients.
abstract: BACKGROUND
  Mucosal-associated invariant T (MAIT) cells play an important role in innate host defence. MAIT cells appear to undergo exhaustion and are functionally weakened in chronic viral infections. However, their role in chronic hepatitis C virus (HCV) infection remains unclear.
  
  
  METHODS
  We investigated the frequency of CD8(+) CD161(++) TCR Vα7.2(+) MAIT cells in a cross-sectional cohort of chronic HCV-infected patients (n = 25) and healthy controls (n = 25). Peripheral blood mononuclear cells were investigated for circulating MAIT cell frequency, liver-homing (CCR5 and CD103), biomarkers of immune exhaustion (PD-1, TIM-3 and CTLA-4), chronic immune activation (CD38 and HLA-DR), and immunosenescence (CD57) by flow cytometry.
  
  
  RESULTS
  The frequency of MAIT cells was significantly decreased, and increased signs of immune exhaustion and chronic immune activation were clearly evident on MAIT cells of HCV-infected patients. Decrease of CCR5 on circulating MAIT cells is suggestive of their peripheral loss in chronic HCV-infected patients. MAIT cells also showed significantly increased levels of HLA-DR, CD38, PD-1, TIM-3 and CTLA-4, besides CD57 in chronic HCV disease.
  
  
  CONCLUSIONS
  Immune exhaustion and senescence of CD8(+) CD161(++) TCR Vα7.2(+) MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression.
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Muttiah
authors.initials: M
authors.lastname: Barathan
authors.affiliation: Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rosmawati
authors.initials: R
authors.lastname: Mohamed
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Jamuna
authors.initials: J
authors.lastname: Vadivelu
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Li Y
authors.initials: LY
authors.lastname: Chang
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Alireza
authors.initials: A
authors.lastname: Saeidi
authors.affiliation: Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Yean K
authors.initials: YK
authors.lastname: Yong
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: M
authors.initials: M
authors.lastname: Ravishankar Ram
authors.affiliation: Department of Orthopaedic Surgery, Tissue Engineering Group (TEG), NOCERAL, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kaliappan
authors.initials: K
authors.lastname: Gopal
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Atlanta, GA, USA.
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Velu
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Esaki M
authors.initials: EM
authors.lastname: Shankar
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D015415:Biomarkers; D018959:CD57 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D000068884:Immunosenescence / Q000276:immunology; D039001:Integrin alpha Chains / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D019713:Receptors, CCR5 / Q000276:immunology; D019562:Viral Load; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C584933:CCR5 protein, human; D018959:CD57 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C448908:HAVCR2 protein, human; D006684:HLA-DR Antigens; D000072597:Hepatitis A Virus Cellular Receptor 2; D039001:Integrin alpha Chains; C527203:KLRB1 protein, human; D008565:Membrane Proteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019713:Receptors, CCR5; C091367:alpha E integrins; D051997:ADP-ribosyl Cyclase 1
keywords: CD38; HCV infection; MAIT cells; PD-1; TCRVα7.2; exhaustion