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. 2024 Jun 21;9(96):eadj8526.
doi: 10.1126/sciimmunol.adj8526. Epub 2024 Jun 21.

SARS-CoV-2 inflammation durably imprints memory CD4 T cells

Sophie L Gray-Gaillard  1 , Sabrina M Solis  1 , Han M Chen  1 , Clarice Monteiro  1 , Grace Ciabattoni  2 , Marie I Samanovic  1 , Amber R Cornelius  1 , Tijaana Williams  1 , Emilie Geesey  1 , Miguel Rodriguez  1 , Mila Brum Ortigoza  1 , Ellie N Ivanova  3 , Sergei B Koralov  3 , Mark J Mulligan  1   2 , Ramin Sedaghat Herati  1   2
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SARS-CoV-2 inflammation durably imprints memory CD4 T cells

Sophie L Gray-Gaillard et al. Sci Immunol. .

Erratum in

Abstract

Memory CD4 T cells are critical to human immunity, yet it is unclear whether viral inflammation during memory formation has long-term consequences. Here, we compared transcriptional and epigenetic landscapes of Spike (S)-specific memory CD4 T cells in 24 individuals whose first exposure to S was via SARS-CoV-2 infection or mRNA vaccination. Nearly 2 years after memory formation, S-specific CD4 T cells established by infection remained enriched for transcripts related to cytotoxicity and for interferon-stimulated genes, likely because of a chromatin accessibility landscape altered by inflammation. Moreover, S-specific CD4 T cells primed by infection had reduced proliferative capacity in vitro relative to vaccine-primed cells. Furthermore, the transcriptional state of S-specific memory CD4 T cells was minimally altered by booster immunization and/or breakthrough infection. Thus, infection-associated inflammation durably imprints CD4 T cell memory, which affects the function of these cells and may have consequences for long-term immunity.

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