Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease

Zhongfang Wang, Lingyan Zhu, Thi H. O. Nguyen, Yanmin Wan, Sneha Sant, Sergio M. Quiñones-Parra, Jeremy Chase Crawford, Auda A. Eltahla, Simone Rizzetto, Rowena A. Bull, Chenli Qiu, Marios Koutsakos, E. Bridie Clemens, Liyen Loh, Tianyue Chen, Lu Liu, Pengxing Cao, Yanqin Ren, Lukasz Kedzierski, Tom Kotsimbos, James M. McCaw, Nicole L. Gruta, Stephen J. Turner, Allen C. Cheng, Fabio Luciani, Xiaoyan Zhang, Peter C. Doherty, Paul G. Thomas, Jianqing Xu () and Katherine Kedzierska ()
Additional contact information
Zhongfang Wang: Fudan University
Lingyan Zhu: Fudan University
Thi H. O. Nguyen: The Peter Doherty Institute for Infection and Immunity
Yanmin Wan: Fudan University
Sneha Sant: The Peter Doherty Institute for Infection and Immunity
Sergio M. Quiñones-Parra: The Peter Doherty Institute for Infection and Immunity
Jeremy Chase Crawford: St. Jude Children’s Research Hospital
Auda A. Eltahla: UNSW Sydney
Simone Rizzetto: UNSW Sydney
Rowena A. Bull: UNSW Sydney
Chenli Qiu: Fudan University
Marios Koutsakos: The Peter Doherty Institute for Infection and Immunity
E. Bridie Clemens: The Peter Doherty Institute for Infection and Immunity
Liyen Loh: The Peter Doherty Institute for Infection and Immunity
Tianyue Chen: Fudan University
Lu Liu: Fudan University
Pengxing Cao: University of Melbourne
Yanqin Ren: Fudan University
Lukasz Kedzierski: The Peter Doherty Institute for Infection and Immunity
Tom Kotsimbos: Alfred Hospital Health and Department Medicine, Monash University
James M. McCaw: University of Melbourne
Nicole L. Gruta: The Peter Doherty Institute for Infection and Immunity
Stephen J. Turner: The Peter Doherty Institute for Infection and Immunity
Allen C. Cheng: Alfred Health and School of Public Health and Preventive Medicine
Fabio Luciani: UNSW Sydney
Xiaoyan Zhang: Fudan University
Peter C. Doherty: The Peter Doherty Institute for Infection and Immunity
Paul G. Thomas: St. Jude Children’s Research Hospital
Jianqing Xu: Fudan University
Katherine Kedzierska: Fudan University

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8+ T-cell profiles from patients hospitalized with avian H7N9, seasonal IAV, and influenza vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38+HLA-DR+PD-1+ CD8+ T cells, whereas the prolonged persistence of this set is found in ultimately fatal cases. Single-cell T cell receptor (TCR)-αβ analyses of activated CD38+HLA-DR+CD8+ T cells show similar TCRαβ diversity but differential clonal expansion kinetics in surviving and fatal H7N9 patients. Delayed clonal expansion associated with an early dichotomy at a transcriptome level (as detected by single-cell RNAseq) is found in CD38+HLA-DR+CD8+ T cells from patients who succumbed to the disease, suggesting a divergent differentiation pathway of CD38+HLA-DR+CD8+ T cells from the outset during fatal disease. Our study proposes that effective expansion of cross-reactive influenza-specific TCRαβ clonotypes with appropriate transcriptome signatures is needed for early protection against severe influenza disease.

Date: 2018
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DOI: 10.1038/s41467-018-03243-7

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