SARS-CoV-2 inflammation durably imprints memory CD4 T cells
Sophie L. Gray-Gaillard, Sabrina Solis, H. Chen, Clarice Monteiro, Grace O. Ciabattoni, Marie I. Samanovic, Amber Cornelius, Tijaana Williams, Emilie Geesey, Miguel Rodríguez, Mila B. Ortigoza, Ellie Ivanova, Sergei B. Koralov, Mark J. Mulligan, Ramin S. Herati
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.