Post by Nadica (She/Her) on Jun 23, 2024 3:22:43 GMT
SARS-CoV-2 inflammation durably imprints memory CD4 T cells - Published June 21, 2024
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
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
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.