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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320007

ABSTRACT

Memory T-cell responses have been demonstrated after recovery from SARS-CoV-2 infection, but the phenotypes of SARS-CoV-2-specific T cells have not been comprehensively investigated ex vivo. We detected SARS-CoV-2-specific CD8+ T cells by MHC-I multimer staining and examined their phenotypes in relation to their functional capacity in acute and convalescent COVID-19. In the convalescent phase, multimer+ cells exhibited early differentiated effector-memory phenotypes. The frequency of CD127+KLRG1- memory precursor effector cells among multimer+ cells was significantly lower in convalescent individuals with severe disease than those with mild disease. Cytokine-secretion assays combined with MHC-I multimer staining revealed that the proportion of IFN-γ-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to other viruses. Importantly, the proportion of IFN-γ-producing cells was significantly higher in PD-1+ cells than PD-1- cells among multimer+ cells in both the acute and convalescence phases, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our findings provide insights for effective vaccine development.

2.
Immunity ; 54(1): 44-52.e3, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-1065202

ABSTRACT

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.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Programmed Cell Death 1 Receptor/metabolism , SARS-CoV-2/immunology , Acute-Phase Reaction/immunology , Acute-Phase Reaction/virology , COVID-19/pathology , COVID-19/virology , Convalescence , Epitopes, T-Lymphocyte , Histocompatibility Antigens Class I/immunology , Humans , Immunologic Memory , Immunophenotyping , Interferon-gamma/metabolism , Lymphocyte Activation , Viral Load
3.
Immunity ; 54(1): 44-52.e3, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-988082

ABSTRACT

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.


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