title: Severe pandemic H1N1 2009 infection is associated with transient NK and T deficiency and aberrant CD8 responses.
abstract: BACKGROUND
  It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection.
  
  
  RESULTS
  49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts.
  
  
  CONCLUSIONS
  Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired.
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Dong Da, Ha Noi, Viet Nam. afox@oucru.org
authors.forename: Annette
authors.initials: A
authors.lastname: Fox
authors.forename: Nguyen Minh Hoa
authors.initials: NM
authors.lastname: Le
authors.forename: Peter
authors.initials: P
authors.lastname: Horby
authors.forename: H Rogier
authors.initials: HR
authors.lastname: van Doorn
authors.forename: Vu Trung
authors.initials: VT
authors.lastname: Nguyen
authors.forename: Hong Ha
authors.initials: HH
authors.lastname: Nguyen
authors.forename: Trung Cap
authors.initials: TC
authors.lastname: Nguyen
authors.forename: Dinh Phu
authors.initials: DP
authors.lastname: Vu
authors.forename: Minh Ha
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Nguyen Thi Ngoc
authors.initials: NT
authors.lastname: Diep
authors.forename: Vu Thi Ngoc
authors.initials: VT
authors.lastname: Bich
authors.forename: Huong Tran Thi Kieu
authors.initials: HT
authors.lastname: Huong
authors.forename: Walter R
authors.initials: WR
authors.lastname: Taylor
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Heiman
authors.initials: H
authors.lastname: Wertheim
authors.forename: Van Kinh
authors.initials: VK
authors.lastname: Nguyen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000276:immunology* / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D058873:Pandemics / Q000706:statistics & numerical data*; D012367:RNA, Viral / Q000032:analysis; D014744:Vietnam / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D012367:RNA, Viral