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

Zhongfang Wang, Yanmin Wan, Chenli Qiu, Sergio Quiñones-Parra, Zhaoqin Zhu, Liyen Loh, Di Tian, Yanqin Ren, Yunwen Hu, Xiaoyan Zhang, Paul G. Thomas, Michael Inouye, Peter C. Doherty, Katherine Kedzierska () and Jianqing Xu ()
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Zhongfang Wang: 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
Yanmin Wan: 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
Chenli Qiu: 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
Sergio Quiñones-Parra: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Zhaoqin Zhu: 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
Liyen Loh: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Di Tian: 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
Yanqin Ren: 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
Yunwen Hu: 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
Xiaoyan Zhang: 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
Paul G. Thomas: St Jude Children’s Research Hospital
Michael Inouye: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Peter C. Doherty: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Katherine Kedzierska: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Jianqing Xu: 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

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7833

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