title: High levels of virus-specific CD4+ T cells predict severe pandemic influenza A virus infection.
abstract: BACKGROUND
  T-cell responses have been implicated in control and exacerbation of lung injury during influenza A virus (IAV) infection.
  
  
  OBJECTIVE
  To examine the breadth and magnitude of influenza-specific CD4(+) and CD8(+) T-cell responses during acute phase of infection.
  
  
  METHODS
  Influenza-specific T-cell response to the entire pandemic H1N1/09 IAV proteome and T cell-related cytokine levels were measured in blood from previously healthy individuals with mild (n = 32) and severe (n = 16) IAV infection during the 2009 influenza pandemic. Virus-specific T-cell response in lung and blood was also performed in two acutely infected, severely ill patients using fluorescent-conjugated pdmH1N1/09 Matrix-MHC-I tetrameric complexes.
  
  
  RESULTS
  Strong and broad CD4(+) but not CD8(+) T-cell responses were observed in the blood, and were higher in those with severe disease. Antigen-specific CD8(+) T cells in the lungs were on average 45-fold higher compared with blood in severely ill patients. Paradoxically, in patients with severe disease, IL-17, IL-2, IL-4, and IFN-γ levels were significantly decreased.
  
  
  CONCLUSIONS
  High levels of circulating virus-specific CD4(+) T cells to two viral internal proteins (nucleoprotein and matrix) in the first phase of infection are associated with subsequent development of severe IAV infection. This finding could be an early and specific marker for ensuing clinical deterioration. Contrasting levels of antigen-specific CD8(+) T cells in lungs and blood have implications on design and analysis of clinical trials for T-cell vaccines because measurements of T cells in the periphery may not reflect events in the lungs.
authors.affiliation: Beijing You’an Hospital, Capital Medical University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Laura
authors.initials: L
authors.lastname: Denney
authors.forename: Duncan
authors.initials: D
authors.lastname: Young
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Powell
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Peng
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Yan
authors.forename: Da-Yan
authors.initials: DY
authors.lastname: Wang
authors.forename: Yue-Long
authors.initials: YL
authors.lastname: Shu
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kendrick
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Ling-Pei
authors.initials: LP
authors.lastname: Ho
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D018893:Bronchoalveolar Lavage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002681:China / Q000453:epidemiology; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D058873:Pandemics; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers