Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia

Nat Commun. 2020 Jul 6;11(1):3434. doi: 10.1038/s41467-020-17292-4.

Abstract

The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients' T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1+CD57+ exhausted T cells. Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors. Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4+ T cells from both groups. Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-γ, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Betacoronavirus / immunology*
  • Biomarkers / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • COVID-19
  • Cellular Senescence
  • Coronavirus Infections / blood
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / pathology
  • Cytokine Release Syndrome
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Humans
  • Immunologic Memory
  • Italy / epidemiology
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / pathology
  • SARS-CoV-2
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Th17 Cells / pathology

Substances

  • Biomarkers
  • Cytokines