Journal Article

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

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

2018

Overview

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. Virus-specific CD8 + T cells are crucial during H7N9 influenza infection, but CD8 + T cell dysfunction is associated with poor prognosis. Here, the authors use molecular and phenotypic analysis to establish persistence of clonally diverse CD8 + T cell populations during fatal infection.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/91 / 45/91 / 49/88 / 631/250/1619/554/1775 / 631/250/1619/554/1834 / 631/250/255/1578 / 631/250/255/2514 / 82/1 / ADP-ribosyl Cyclase 1 - genetics / ADP-ribosyl Cyclase 1 - immunology / CD38 antigen / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - pathology / CD8-Positive T-Lymphocytes - virology / Clonal Selection, Antigen-Mediated - genetics / Cohort Studies / Critical Illness / Gene expression / Gene Expression Regulation / Histocompatibility antigen HLA / HLA-DR Antigens - genetics / HLA-DR Antigens - immunology / Hospitalization / Humanities and Social Sciences / Humans / Influenza / Influenza A / Influenza A Virus, H7N9 Subtype - immunology / Influenza A Virus, H7N9 Subtype - pathogenicity / Influenza, Human - genetics / Influenza, Human - immunology / Influenza, Human - mortality / Influenza, Human - virology / Lymphocyte Activation / Lymphocytes / Lymphocytes T / Membrane Glycoproteins - genetics / Membrane Glycoproteins - immunology / multidisciplinary / Patients / PD-1 protein / Programmed Cell Death 1 Receptor - genetics / Programmed Cell Death 1 Receptor - immunology / Reaction kinetics / Receptors, Antigen, T-Cell, alpha-beta - genetics / Receptors, Antigen, T-Cell, alpha-beta - immunology / Science / Science (multidisciplinary) / Survival Analysis / T cell receptors / T-Lymphocyte Subsets - immunology / T-Lymphocyte Subsets - pathology / T-Lymphocyte Subsets - virology / Transcriptome - immunology / Viruses