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

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

Author information

1
1] Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China [2] Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville 3010, Victoria, Australia.
2
Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China.
3
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville 3010, Victoria, Australia.
4
Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennesse 38105, USA.
5
1] Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville 3010, Victoria, Australia [2] Medical Systems Biology, Department of Pathology, University of Melbourne, Parkville, 3010, Australia.
6
1] Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville 3010, Victoria, Australia [2] Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennesse 38105, USA.

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.

PMID:
25967273
PMCID:
PMC4479016
DOI:
10.1038/ncomms7833
[Indexed for MEDLINE]
Free PMC Article

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