PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19

Immunity. 2021 Jan 12;54(1):44-52.e3. doi: 10.1016/j.immuni.2020.12.002. Epub 2020 Dec 14.


Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.

Keywords: CD8(+) T cell; COVID-19; IFN-γ; MHC class I multimer; Memory T cell; PD-1; SARS-CoV-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / immunology
  • Acute-Phase Reaction / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Convalescence
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Interferon-gamma / metabolism
  • Lymphocyte Activation
  • Programmed Cell Death 1 Receptor / metabolism*
  • SARS-CoV-2 / immunology*
  • Viral Load


  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • IFNG protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Interferon-gamma