Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8⁺ T cells

Nat Commun. 2015 May 13;6:6833. doi: 10.1038/ncomms7833.

Abstract

The avian origin A/H7N9 influenza virus causes high admission rates (>99%) and mortality (>30%), with ultimately favourable outcomes ranging from rapid recovery to prolonged hospitalization. Using a multicolour assay for monitoring adaptive and innate immunity, here we dissect the kinetic emergence of different effector mechanisms across the spectrum of H7N9 disease and recovery. We find that a diversity of response mechanisms contribute to resolution and survival. Patients discharged within 2-3 weeks have early prominent H7N9-specific CD8(+) T-cell responses, while individuals with prolonged hospital stays have late recruitment of CD8(+)/CD4(+) T cells and antibodies simultaneously (recovery by week 4), augmented even later by prominent NK cell responses (recovery >30 days). In contrast, those who succumbed have minimal influenza-specific immunity and little evidence of T-cell activation. Our study illustrates the importance of robust CD8(+) T-cell memory for protection against severe influenza disease caused by newly emerging influenza A viruses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / blood
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes / physiology*
  • Humans
  • Influenza A Virus, H7N9 Subtype*
  • Influenza, Human / immunology
  • Influenza, Human / pathology*
  • Influenza, Human / virology*
  • Leukocytes, Mononuclear / physiology
  • Oligonucleotide Array Sequence Analysis
  • Receptors, KIR2DL1

Substances

  • Antibodies, Viral
  • Receptors, KIR2DL1