%0 Journal Article
%T SARS-CoV-2 inflammation durably imprints memory CD4 T cells.
%A Gray-Gaillard SL
%A Solis SM
%A Chen HM
%A Monteiro C
%A Ciabattoni G
%A Samanovic MI
%A Cornelius AR
%A Williams T
%A Geesey E
%A Rodriguez M
%A Ortigoza MB
%A Ivanova EN
%A Koralov SB
%A Mulligan MJ
%A Herati RS
%J Sci Immunol
%V 9
%N 96
%D 2024 Jun 21
%M 38905326
%F 30.63
%R 10.1126/sciimmunol.adj8526
%X 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.