| Title: |
Polyfunctional T peripheral helper cells are associated with the magnitude and durability of antibody responses after COVID‐19. |
| Authors: |
Tungatt, Katie; Gomes, Gabriela Martins Costa; Fewings, Nicole L; Stubis, Aija; Doyle, Chloe M; Merheb, Vera; Aggarwal, Anupriya; Byth, Karen; Robertson, Harry; Dervish, Suat; Maddocks, Susan; Taylor, Janette; Bull, Rowena A; Martinello, Marianne; Brilot, Fabienne; Turville, Stuart G; Cunningham, Anthony L; Sandgren, Kerrie J |
| Source: |
Clinical & Translational Immunology; 2025, Vol. 14 Issue 12, p1-17, 17p |
| Subject Terms: |
T helper cells; COVID-19; Interleukin-6; Antibody formation; Vaccine effectiveness; SARS-CoV-2; Humoral immunity |
| 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. [ABSTRACT FROM AUTHOR] |
| : |
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| Database: |
Complementary Index |