{Reference Type}: Journal Article
{Title}: SARS-CoV-2 inflammation durably imprints memory CD4 T cells.
{Author}: Gray-Gaillard SL;Solis SM;Chen HM;Monteiro C;Ciabattoni G;Samanovic MI;Cornelius AR;Williams T;Geesey E;Rodriguez M;Ortigoza MB;Ivanova EN;Koralov SB;Mulligan MJ;Herati RS;
{Journal}: Sci Immunol
{Volume}: 9
{Issue}: 96
{Year}: 2024 Jun 21
{Factor}: 30.63
{DOI}: 10.1126/sciimmunol.adj8526
{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.