CD8+PD-L1+CXCR3+ polyfunctional T cell abundances are associated with survival in critical SARS-CoV-2-infected patients

JCI Insight. 2021 Sep 22;6(18):e151571. doi: 10.1172/jci.insight.151571.

Abstract

The importance of the adaptive T cell response in the control and resolution of viral infection has been well established. However, the nature of T cell-mediated viral control mechanisms in life-threatening stages of COVID-19 has yet to be determined. The aim of the present study was to determine the function and phenotype of T cell populations associated with survival or death of patients with COVID-19 in intensive care as a result of phenotypic and functional profiling by mass cytometry. Increased frequencies of circulating, polyfunctional CD4+CXCR5+HLA-DR+ stem cell memory T cells (Tscms) and decreased proportions of granzyme B-expressing and perforin-expressing effector memory T cells were detected in recovered and deceased patients, respectively. The higher abundance of polyfunctional PD-L1+CXCR3+CD8+ effector T cells (Teffs), CXCR5+HLA-DR+ Tscms, and anti-nucleocapsid (anti-NC) cytokine-producing T cells permitted us to differentiate between recovered and deceased patients. The results from a principal component analysis show an imbalance in the T cell compartment that allowed for the separation of recovered and deceased patients. The paucity of circulating PD-L1+CXCR3+CD8+ Teffs and NC-specific CD8+ T cells accurately forecasts fatal disease outcome. This study provides insight into the nature of the T cell populations involved in the control of COVID-19 and therefore might impact T cell-based vaccine designs for this infectious disease.

Keywords: Adaptive immunity; Immunology; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B7-H1 Antigen / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8 Antigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / immunology*
  • COVID-19 / mortality
  • COVID-19 / pathology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • France / epidemiology
  • Humans
  • Immunity, Cellular*
  • Immunologic Memory
  • Lymphocyte Activation
  • Male
  • Receptors, CXCR3 / immunology*
  • SARS-CoV-2
  • Survival Rate / trends

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • CD8 Antigens
  • CXCR3 protein, human
  • Epitopes, T-Lymphocyte
  • Receptors, CXCR3

Grants and funding

The study was supported by Fondation de France, « Tous unis contre le virus » framework Alliance (Fondation de France, AP-HP, Institut Pasteur) in collaboration with Agence Nationale de la Recherche (ANR Flash COVID19 program), and by the SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University (I-COVID programs). BC laboratory is supported by grants from AG2R LA MONDIALE (Region IDF, France), Fondation pour la Recherche Médicale (FRM) team award. LA and PR are recipient of post-doctoral fellowships from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 681137 and ANR Flash COVID19 program.