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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.
Cell Mol Immunol ; 18(10): 2325-2333, 2021 10.
Article in English | MEDLINE | ID: covidwho-1366812

ABSTRACT

In addition to CD4+ T cells and neutralizing antibodies, CD8+ T cells contribute to protective immune responses against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. In patients with COVID-19, CD8+ T cells exhibiting activated phenotypes are commonly observed, although the absolute number of CD8+ T cells is decreased. In addition, several studies have reported an upregulation of inhibitory immune checkpoint receptors, such as PD-1, and the expression of exhaustion-associated gene signatures in CD8+ T cells from patients with COVID-19. However, whether CD8+ T cells are truly exhausted during COVID-19 has been a controversial issue. In the present review, we summarize the current understanding of CD8+ T-cell exhaustion and describe the available knowledge on the phenotypes and functions of CD8+ T cells in the context of activation and exhaustion. We also summarize recent reports regarding phenotypical and functional analyses of SARS-CoV-2-specific CD8+ T cells and discuss long-term SARS-CoV-2-specific CD8+ T-cell memory.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Humans , Immunologic Memory , Lymphocyte Activation , Lymphocyte Count
3.
Nat Commun ; 12(1): 4043, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1290767

ABSTRACT

Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. Here we conduct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescent patients up to 317 days post-symptom onset (DPSO), and find that memory T cell responses are maintained during the study period regardless of the severity of COVID-19. In particular, we observe sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells is increased, peaking at approximately 120 DPSO. Development of TSCM cells is confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19, thus support the feasibility of effective vaccination programs as a measure for COVID-19 control.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunologic Memory/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Enzyme-Linked Immunosorbent Assay , Humans , Interferon-gamma/blood , Vaccination
4.
Immune Netw ; 21(1): e2, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1138867

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. In the current review, we describe SARS-CoV-2-specific CD4+ and CD8+ T-cell responses in acute and convalescent COVID-19 patients. We also discuss the relationships between COVID-19 severity and SARS-CoV-2-specific T-cell responses and summarize recent reports regarding SARS-CoV-2-reactive T cells in SARS-CoV-2-unexposed individuals. These T cells may be cross-reactive cells primed by previous infection with human common-cold coronaviruses. Finally, we outline SARS-CoV-2-specific T-cell responses in the context of vaccination. A better understanding of SARS-CoV-2-specific T-cell responses is needed to develop effective vaccines and therapeutics.

5.
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
6.
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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