Article
TNF-α+ CD4+ T cells dominate the SARS-CoV-2 specific T cell response in COVID-19 outpatients and are associated with durable antibodies

https://doi.org/10.1016/j.xcrm.2022.100640Get rights and content
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Highlights

  • SARS-CoV-2-specific CD4+ response shifts from cells producing IFNγ to TNF-α

  • SARS-CoV-2-specific IFNγTNF-α+ CD4+ T cells predominate at later timepoints

  • IFNγ-TNF-α+ CD4+ T cells correlate with durable SARS-CoV-2-neutralizing antibodies

  • Post-infection mRNA vaccination boosts both IFNγ+ and TNF-α+ S-specific CD4+ T cells

Summary

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4+ T cells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4+ longitudinal dynamics following infection and of specific features that correlate with the maintenance of neutralizing antibodies remains limited. Here, we characterize SARS-CoV-2-specific CD4+ T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4+ response shifts from cells producing interferon gamma (IFNγ) to tumor necrosis factor alpha (TNF-α) from 5 days to 4 months post-enrollment, with IFNγ-IL-21-TNF-α+ CD4+ T cells the predominant population detected at later time points. Greater percentages of IFNγ-IL-21-TNF-α+ CD4+ T cells on day 28 correlate with SARS-CoV-2-neutralizing antibodies measured 7 months post-infection (⍴ = 0.4, p = 0.01). mRNA vaccination following SARS-CoV-2 infection boosts both IFNγ- and TNF-α-producing, spike-protein-specific CD4+ T cells. These data suggest that SARS-CoV-2-specific, TNF-α-producing CD4+ T cells may play an important role in antibody maintenance following COVID-19.

Keywords

CD4
T cells
COVID-19
SARS-CoV-2
antibodies
Tfh
cytokines
neutralizing antibodies
TNF-α
longitudinal

Data and code availability

  • RNA sequencing data have been deposited at NCBI Gene Expression Omnibus and are publicly available as of the date of publication. The accession number is listed in the key resources table.

  • The Olink, clinical, virological, and immunological data, as well as the source codes, have been deposited the GitHub repository and are publicly available as of the date of publication. The GitHub link is listed in the key resources table.

  • Additional supplemental items are available from Mendeley Data: https://doi.org/10.17632/nzd3f5c3j4.1.

  • Other underlying data for this paper will be shared by the lead contact upon request without restriction.

Cited by (0)

10

These authors contributed equally

11

Lead contact