title: Chronic ethanol exposure selectively inhibits the influenza-specific CD8 T cell response during influenza a virus infection.
abstract: BACKGROUND
  It is well established that chronic ethanol (EtOH) consumption is associated with increased incidence and disease severity of respiratory infections. Our recent work demonstrates this increase in disease severity to influenza A virus (IAV) infections is due, in part, to a failure to mount a robust IAV-specific CD8 T cell response along with a specific impairment in the ability of these T cells to produce interferon γ (IFNγ). However, the full extent of the lesion in the effector CD8 T cell compartment during chronic EtOH consumption remains unknown.
  
  
  METHODS
  Utilizing the Meadows-Cook murine model of chronic alcohol consumption, mice received EtOH in their drinking water for 8 or 12 weeks. Mice were challenged intranasally with IAV, and the activation and effector functions of IAV-specific CD8 T cells were determined in both the lung-draining lymph nodes (dLN) and lungs.
  
  
  RESULTS
  Our results confirm the defect in IFNγ production; however, the ability of IAV-specific T cells to produce tumor necrosis factor α (TNFα) and interleukin-2 (IL-2) in EtOH-consuming mice remains unaltered. In contrast, EtOH consumption significantly reduces the ability of CD8 T cells to degranulate and kill IAV-specific targets. Finally, our findings suggest the lesion begins during the initial activation of CD8 T cells, as we observe early defects in proliferation in the dLN of IAV-infected, EtOH-consuming mice.
  
  
  CONCLUSIONS
  These findings highlight the previously unrecognized depth of the lesion in the IAV-specific CD8 T cell response during chronic EtOH consumption. Given the important role CD8 T cell immunity plays in control of IAV, these findings may aid in the development of vaccination and/or therapeutic strategies to reverse these defects in the CD8 T cell response and reduce serious disease outcomes associated with IAV infections in alcoholics.
authors.affiliation: Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Hemann
authors.forename: Jodi L
authors.initials: JL
authors.lastname: McGill
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Legge
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000378:metabolism*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage* / Q000633:toxicity; D018836:Inflammation Mediators / Q000378:metabolism; D009980:Influenza A virus / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D000431:Ethanol
keywords: CD8 T Cells; Chronic Ethanol Consumption; Influenza Virus; Lung; Lymph Node