| Autor: |
Gray-Gaillard, Sophie L., Solis, Sabrina M., Chen, Han M., Monteiro, Clarice, Ciabattoni, Grace, Samanovic, Marie I., Cornelius, Amber R., Williams, Tijaana, Geesey, Emilie, Rodriguez, Miguel, Ortigoza, Mila Brum, Ivanova, Ellie N., Koralov, Sergei B., Mulligan, Mark J., Herati, Ramin Sedaghat |
| Předmět: |
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| Zdroj: |
Science Immunology; 2024, Vol. 9 Issue 96, p1-16, 16p |
| Abstrakt: |
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. Editor's summary: It is unclear whether the memory CD4 T cells generated via mRNA vaccination and via SARS-CoV-2 infection are comparable in terms of frequency and function. Gray-Gaillard et al. performed single-cell analysis of spike protein (S)–specific memory CD4 T cells taken from a longitudinal sample of individuals variously vaccinated against SARS-CoV-2 or naturally infected with the virus. Infection-primed S-specific memory CD4 T cells exhibited a durable transcriptional and epigenetic signature of inflammation, a cytotoxic profile, and a proliferative disadvantage compared with vaccine-primed memory CD4 T cells. Breakthrough infections did not generally alter the transcriptional profile of vaccine-primed memory T cells, although re-exposure to antigen accompanied by high levels of inflammation could alter the transcriptional profiles of these cells in a clonotype-specific manner. —Seth Thomas Scanlon [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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