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Nat Commun. 2018 Feb 26;9(1):824. doi: 10.1038/s41467-018-03243-7.
Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease.
Wang Z1,2, Zhu L1, Nguyen THO2, Wan Y1, Sant S2, Qui?ones-Parra SM2, Crawford JC3, Eltahla AA4, Rizzetto S4, Bull RA4, Qiu C1, Koutsakos M2, Clemens EB2, Loh L2, Chen T1, Liu L1, Cao P5, Ren Y1, Kedzierski L2, Kotsimbos T6, McCaw JM5, La Gruta NL2,7, Turner SJ2,8, Cheng AC9, Luciani F4, Zhang X1, Doherty PC2,3, Thomas PG3, Xu J10, Kedzierska K11,12.
Author information
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.
PMID: 29483513 DOI: 10.1038/s41467-018-03243-7
Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease.
Wang Z1,2, Zhu L1, Nguyen THO2, Wan Y1, Sant S2, Qui?ones-Parra SM2, Crawford JC3, Eltahla AA4, Rizzetto S4, Bull RA4, Qiu C1, Koutsakos M2, Clemens EB2, Loh L2, Chen T1, Liu L1, Cao P5, Ren Y1, Kedzierski L2, Kotsimbos T6, McCaw JM5, La Gruta NL2,7, Turner SJ2,8, Cheng AC9, Luciani F4, Zhang X1, Doherty PC2,3, Thomas PG3, Xu J10, Kedzierska K11,12.
Author information
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.
PMID: 29483513 DOI: 10.1038/s41467-018-03243-7