title: Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8⁺ T cells.
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.
authors.affiliation: 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.
authors.forename: Zhongfang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Wan
authors.affiliation: 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.
authors.forename: Chenli
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville 3010, Victoria, Australia.
authors.forename: Sergio
authors.initials: S
authors.lastname: Quiñones-Parra
authors.affiliation: 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.
authors.forename: Zhaoqin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville 3010, Victoria, Australia.
authors.forename: Liyen
authors.initials: L
authors.lastname: Loh
authors.affiliation: 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.
authors.forename: Di
authors.initials: D
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Ren
authors.affiliation: 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.
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennesse 38105, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.affiliation: 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.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doherty
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville 3010, Victoria, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
authors.affiliation: 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.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype; D007251:Influenza, Human / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D054342:Receptors, KIR2DL1
chemical_list: D000914:Antibodies, Viral; D054342:Receptors, KIR2DL1