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 & 10 others James M. McCaw, Nicole L. La Gruta, Stephen J. Turner, Allen C. Cheng, Fabio Luciani, Xiaoyan Zhang, Peter C. Doherty, Paul G. Thomas, Jianqing Xu, Katherine Kedzierska

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number824
Number of pages12
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 26 Feb 2018

Keywords

  • CD8-positive T cells
  • infuenza virus
  • T-cell receptor
  • viral infection

Cite this

Wang, Z., Zhu, L., Nguyen, T. H. O., Wan, Y., Sant, S., Quiñones-Parra, S. M., ... Kedzierska, K. (2018). Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease. Nature Communications, 9(1), [824]. https://doi.org/10.1038/s41467-018-03243-7
Wang, Zhongfang ; Zhu, Lingyan ; Nguyen, Thi H.O. ; Wan, Yanmin ; Sant, Sneha ; Quiñones-Parra, Sergio M. ; Crawford, Jeremy Chase ; Eltahla, Auda A. ; Rizzetto, Simone ; Bull, Rowena A. ; Qiu, Chenli ; Koutsakos, Marios ; Clemens, E. Bridie ; Loh, Liyen ; Chen, Tianyue ; Liu, Lu ; Cao, Pengxing ; Ren, Yanqin ; Kedzierski, Lukasz ; Kotsimbos, Tom ; McCaw, James M. ; La Gruta, Nicole L. ; Turner, Stephen J. ; Cheng, Allen C. ; Luciani, Fabio ; Zhang, Xiaoyan ; Doherty, Peter C. ; Thomas, Paul G. ; Xu, Jianqing ; Kedzierska, Katherine. / Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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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.",
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Wang, Z, Zhu, L, Nguyen, THO, Wan, Y, Sant, S, Quiñones-Parra, SM, Crawford, JC, Eltahla, AA, Rizzetto, S, Bull, RA, Qiu, C, Koutsakos, M, Clemens, EB, Loh, L, Chen, T, Liu, L, Cao, P, Ren, Y, Kedzierski, L, Kotsimbos, T, McCaw, JM, La Gruta, NL, Turner, SJ, Cheng, AC, Luciani, F, Zhang, X, Doherty, PC, Thomas, PG, Xu, J & Kedzierska, K 2018, 'Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease' Nature Communications, vol. 9, no. 1, 824. https://doi.org/10.1038/s41467-018-03243-7

Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease. / Wang, Zhongfang; Zhu, Lingyan; Nguyen, Thi H.O.; Wan, Yanmin; Sant, Sneha; Quiñones-Parra, Sergio M.; Crawford, Jeremy Chase; Eltahla, Auda A.; Rizzetto, Simone; Bull, Rowena A.; Qiu, Chenli; Koutsakos, Marios; Clemens, E. Bridie; Loh, Liyen; Chen, Tianyue; Liu, Lu; Cao, Pengxing; Ren, Yanqin; Kedzierski, Lukasz; Kotsimbos, Tom; McCaw, James M.; La Gruta, Nicole L.; Turner, Stephen J.; Cheng, Allen C.; Luciani, Fabio; Zhang, Xiaoyan; Doherty, Peter C.; Thomas, Paul G.; Xu, Jianqing; Kedzierska, Katherine.

In: Nature Communications, Vol. 9, No. 1, 824, 26.02.2018.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Wang, Zhongfang

AU - Zhu, Lingyan

AU - Nguyen, Thi H.O.

AU - Wan, Yanmin

AU - Sant, Sneha

AU - Quiñones-Parra, Sergio M.

AU - Crawford, Jeremy Chase

AU - Eltahla, Auda A.

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AU - Koutsakos, Marios

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AU - Loh, Liyen

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AU - Liu, Lu

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AU - Ren, Yanqin

AU - Kedzierski, Lukasz

AU - Kotsimbos, Tom

AU - McCaw, James M.

AU - La Gruta, Nicole L.

AU - Turner, Stephen J.

AU - Cheng, Allen C.

AU - Luciani, Fabio

AU - Zhang, Xiaoyan

AU - Doherty, Peter C.

AU - Thomas, Paul G.

AU - Xu, Jianqing

AU - Kedzierska, Katherine

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Y1 - 2018/2/26

N2 - 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.

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Wang Z, Zhu L, Nguyen THO, Wan Y, Sant S, Quiñones-Parra SM et al. Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease. Nature Communications. 2018 Feb 26;9(1). 824. https://doi.org/10.1038/s41467-018-03243-7