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

Nat Commun. 2018 Feb 26;9(1):824. doi: 10.1038/s41467-018-03243-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / genetics
  • ADP-ribosyl Cyclase 1 / immunology
  • 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 Regulation
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology
  • Hospitalization
  • Humans
  • 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
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Survival Analysis
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocyte Subsets / virology
  • Transcriptome / immunology*

Substances

  • HLA-DR Antigens
  • Membrane Glycoproteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell, alpha-beta
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1