Patients Recovering from Severe COVID-19 Develop a Polyfunctional Antigen-Specific CD4+ T Cell Response

Paolini, Annamaria; Borella, Rebecca; Neroni, Anita; Tartaro, Domenico Lo; Mattioli, Marco; Fidanza, Lucia; Nella, Alessia Di; Santacroce, Elena; Gozzi, Licia; Busani, Stefano; Trenti, Tommaso; Meschiari, Marianna; Guaraldi, Giovanni; Girardis, Massimo; Mussini, Cristina; Gibellini, Lara; Biasi, Sara De; Cossarizza, Andrea

doi:10.3390/ijms23148004

Cited by 12 publications

(6 citation statements)

References 48 publications

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“…During natural infection, typically after a couple of weeks, the magnitude of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4 + and CD8 + memory T-cell response peaks at the maximum and is of the order of 0.5% and 0.2% of the repertoire, respectively ( 2 ). CD4 + T cells display a memory profile (including a specific subset formed by stem cell memory) and are able to produce high levels of both IL-2 and T helper (Th)1 cytokines ( 3 – 5 ). CD4 + T-cell response is greater than the CD8 + counterpart ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Detailed characterization of SARS-CoV-2-specific T and B cells after infection or heterologous vaccination

Tartaro

Paolini²,

Mattioli³

et al. 2023

Front. Immunol.

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The formation of a robust long-term antigen (Ag)-specific memory, both humoral and cell-mediated, is created following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. Here, by using polychromatic flow cytometry and complex data analyses, we deeply investigated the magnitude, phenotype, and functionality of SARS-CoV-2-specific immune memory in two groups of healthy subjects after heterologous vaccination compared to a group of subjects who recovered from SARS-CoV-2 infection. We find that coronavirus disease 2019 (COVID-19) recovered patients show different long-term immunological profiles compared to those of donors who had been vaccinated with three doses. Vaccinated individuals display a skewed T helper (Th)1 Ag-specific T cell polarization and a higher percentage of Ag-specific and activated memory B cells expressing immunoglobulin (Ig)G compared to those of patients who recovered from severe COVID-19. Different polyfunctional properties characterize the two groups: recovered individuals show higher percentages of CD4+ T cells producing one or two cytokines simultaneously, while the vaccinated are distinguished by highly polyfunctional populations able to release four molecules, namely, CD107a, interferon (IFN)-γ, tumor necrosis factor (TNF), and interleukin (IL)-2. These data suggest that functional and phenotypic properties of SARS-CoV-2 adaptive immunity differ in recovered COVID-19 individuals and vaccinated ones.

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Section: Introductionmentioning

confidence: 99%

Detailed characterization of SARS-CoV-2-specific T and B cells after infection or heterologous vaccination

Tartaro

Paolini²,

Mattioli³

et al. 2023

Front. Immunol.

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“…CD4 + T cells play a crucial role in effective cellular immunity, and studies have indicated that the selection of HLA class II-restricted antigen targets recognized by CD4 + T cells is of paramount importance for clinical outcome ( 45 – 49 ). CD4 + T cells support B-cell responses in the germinal center, and some CD4 + T cells also have direct antiviral properties similar to those of CD8 + T cells ( 48 , 50 – 52 ). Furthermore, the FluoroSpot results indicated that the B-cell epitope may contain murine CD8 + T-cell epitopes, and the CD8 + T cells were expanded and survived due to the function of effective CD4 + T cells.…”

Section: Discussionmentioning

confidence: 99%

A Synthetic SARS-CoV-2-Derived T-Cell and B-Cell Peptide Cocktail Elicits Full Protection against Lethal Omicron BA.1 Infection in H11-K18-hACE2 Mice

Song

Xiao

et al. 2023

Microbiol Spectr

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Current vaccines based on production of neutralizing antibodies fail to prevent the infection and transmission of SARS-CoV-2 Omicron and its subvariants. Understanding the critical factors and avoiding the disadvantages of vaccine strategies are essential for developing a safe and effective COVID-19 vaccine, which would include a more effective and durable cellular response, minimal effects of viral mutations, rapid production against emerging variants, and good safety.

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“…As an example, in a recent study, the percentage of CD4 + and CD8 + T cells simultaneously producing IFN‐γ, tumor necrosis factor (TNF), interleukin (IL)‐2, IL‐17, and granzyme B and expressing CD107a was measured in patients who had recovered from a mild or severe form of COVID‐19, compared to patients with current mild or severe COVID pneumonia. After 4 months, patients who had recovered from a severe form displayed high proportions of antigen‐specific CD4 + T cells that produce IFN‐γ, TNF, and IL‐2 and were characterized by polyfunctional SARS‐CoV‐2‐specific CD4 + T cells (Paolini et al., 2022). Similar results were observed in those who recovered from a mild form of COVID‐19 pneumonia.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Antigen‐Specific T and B Cells for Monitoring Immune Protection Against SARS‐CoV‐2

et al. 2023

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Immunological memory is the basis of protection against most pathogens. Long‐living memory T and B cells able to respond to specific stimuli, as well as persistent antibodies in plasma and in other body fluids, are crucial for determining the efficacy of vaccination and for protecting from a second infection by a previously encountered pathogen. Antigen‐specific cells are represented at a very low frequency in the blood, and indeed, they can be considered “rare events” present in the memory T‐cell pool. Therefore, such events should be analyzed with careful attention. In the last 20 years, different methods, mostly based upon flow cytometry, have been developed to identify such rare antigen‐specific cells, and the COVID‐19 pandemic has given a dramatic impetus to characterize the immune response against the virus. In this regard, we know that the identification, enumeration, and characterization of SARS‐CoV‐2‐specific T and B cells following infection and/or vaccination require i) the use of specific peptides and adequate co‐stimuli, ii) the use of appropriate inhibitors to avoid nonspecific activation, iii) the setting of appropriate timing for stimulation, and iv) the choice of adequate markers and reagents to identify antigen‐specific cells. Optimization of these procedures allows not only determination of the magnitude of SARS‐CoV‐2‐specific responses but also a comparison of the effects of different combinations of vaccines or determination of the response provided by so‐called “hybrid immunity,” resulting from a combination of natural immunity and vaccine‐generated immunity. Here, we present two methods that are largely used to monitor the response magnitude and phenotype of SARS‐CoV‐2‐specific T and B cells by polychromatic flow cytometry, along with some tips that can be useful for the quantification of these rare events. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Identification of antigen‐specific T cells Basic Protocol 2: Identification of antigen‐specific B cells

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Patients Recovering from Severe COVID-19 Develop a Polyfunctional Antigen-Specific CD4+ T Cell Response

Cited by 12 publications

References 48 publications

Detailed characterization of SARS-CoV-2-specific T and B cells after infection or heterologous vaccination

Detailed characterization of SARS-CoV-2-specific T and B cells after infection or heterologous vaccination

A Synthetic SARS-CoV-2-Derived T-Cell and B-Cell Peptide Cocktail Elicits Full Protection against Lethal Omicron BA.1 Infection in H11-K18-hACE2 Mice

Analysis of Antigen‐Specific T and B Cells for Monitoring Immune Protection Against SARS‐CoV‐2

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