title: Frequencies of Circulating MAIT Cells Are Diminished in Chronic HCV, HIV and HCV/HIV Co-Infection and Do Not Recover during Therapy.
abstract: OBJECTIVE
  Mucosal-associated invariant T (MAIT) cells comprise a subpopulation of T cells that can be activated by bacterial products and cytokines to produce IFN-γ. Since little is known on MAIT cells during HCV infection, we compared their phenotype and function in comparison to HIV and HCV/HIV co-infected patients, and determined the effect of IFN-α-based and direct-acting antiviral therapy on MAIT cells of HCV patients.
  
  
  METHODS
  Blood samples from patients with chronic HCV (CHCV), virologically suppressed HIV, acute HCV/HIV co-infection (AHCV/HIV) and healthy individuals were examined by flowcytometry for phenotype and function of MAIT and NK cells.
  
  
  CONCLUSIONS
  Compared to healthy individuals, the frequency of CD161+Vα7.2+ MAIT cells was significantly decreased in patients with CHCV, HIV and AHCV/HIV co-infection. CD38 expression on MAIT cells was increased in AHCV/HIV patients. MAIT cells were responsive to IFN-α in vitro as evidenced by enhanced frequencies of IFN-γ producing cells. IFN-α-based therapy for CHCV decreased the frequency of IFN-γ+ MAIT cells, which was still observed 24 weeks after successful therapy. Importantly, even after successful IFN-α-based as well as IFN-α-free therapy for CHCV, decreased frequencies of MAIT cells persisted. We show that the frequencies of MAIT cells are reduced in blood of patients with CHCV, HIV and in AHCV/HIV co-infection compared to healthy individuals. Successful therapy for CHCV did not normalize MAIT cell frequencies at 24 weeks follow up. The impact of HIV and HCV infection on the numbers and function of MAIT cells warrant further studies on the impact of viral infections and the antimicrobial function of MAIT cells.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Michelle
authors.initials: M
authors.lastname: Spaan
authors.affiliation: Department of Internal Medicine, Infectious Diseases section Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Sebastiaan J
authors.initials: SJ
authors.lastname: Hullegie
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Boris J B
authors.initials: BJ
authors.lastname: Beudeker
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Kreefft
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Gertine W
authors.initials: GW
authors.lastname: van Oord
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Zwier M A
authors.initials: ZM
authors.lastname: Groothuismink
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Tilborg
authors.affiliation: Department of Internal Medicine, Infectious Diseases section Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Rijnders
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.affiliation: Department of Internal Medicine, Infectious Diseases section Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Mark A A
authors.initials: MA
authors.lastname: Claassen
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Andre
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D060085:Coinfection / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D000072336:Mucosal-Associated Invariant T Cells / Q000187:drug effects / Q000502:physiology*
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D007371:Interferon-gamma