Dataset Information
Polyfunctional T peripheral helper cells are associated with the magnitude and durability of antibody responses after COVID-19.
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ABSTRACT: Objective
Examine the role of T cells in shaping and sustaining humoral immunity to SARS-CoV-2 and identify immune factors associated with durable antibody responses.Methods
Unvaccinated adults (n = 67) with SARS-CoV-2 infection (Wuhan) of any severity were followed longitudinally for up to 14 months. Anti-Spike (S) binding and neutralising antibodies were measured. Bulk T cell IFNγ and IL-2 responses were assessed by Fluorospot to multiple viral proteins. S-specific T-cell subsets and functions were analysed in detail by flow cytometry in a subset of participants (n = 14), combining activation-induced markers (AIMs) and cytokines. Correlations between S-specific T-cell subsets, their polyfunctionality and antibody levels over time were defined.Results
Over 14 months post infection, anti-S IgG and neutralising antibodies declined significantly but remained detectable in > 85% of participants. Bulk T-cell IFNγ and IL-2 responses persisted without significant reduction. However, S-specific CD4 T cells declined over time. A large proportion of these were peripheral helper T cells (Tph; CXCR5-PD-1+), which were the main producers of IL-21 and showed marked polyfunctionality during early convalescence, in contrast to circulating follicular helper T cells (cTfh). The early presence of polyfunctional, IL-21-producing Tph strongly correlated with S-specific IgG and neutralising antibodies early post-infection and predicted neutralising antibody maintenance a year later. Older age correlated with higher Tph and antibody levels.Conclusion
Early S-specific T-cell responses-particularly polyfunctional, IL-21-producing Tph cells-play a key role in sustaining durable antibody levels post-infection, offering insights for future vaccine strategies and understanding long-term immunity.
SUBMITTER: Tungatt K
PROVIDER: S-EPMC12712866 | biostudies-literature | 2025
REPOSITORIES: biostudies-literature
Publications
Polyfunctional T peripheral helper cells are associated with the magnitude and durability of antibody responses after COVID-19.
Clinical & translational immunology 20251218 12
<h4>Objective</h4>Examine the role of T cells in shaping and sustaining humoral immunity to SARS-CoV-2 and identify immune factors associated with durable antibody responses.<h4>Methods</h4>Unvaccinated adults (<i>n</i> = 67) with SARS-CoV-2 infection (Wuhan) of any severity were followed longitudinally for up to 14 months. Anti-Spike (S) binding and neutralising antibodies were measured. Bulk T cell IFNγ and IL-2 responses were assessed by Fluorospot to multiple viral proteins. S-specific T-cel ...[more]
