SARS-CoV-2 inflammation durably imprints memory CD4 T cells.

Area of Science:

• Immunology
• Virology
• Genomics

Background:

• Memory CD4 T cells are crucial for adaptive immunity.
• The long-term effects of inflammation during memory CD4 T cell formation are not well understood.

Purpose of the Study:

• To investigate the durable consequences of SARS-CoV-2 infection-induced inflammation on Spike (S)-specific memory CD4 T cells.
• To compare the transcriptional and epigenetic profiles of memory CD4 T cells primed by infection versus vaccination.

Main Methods:

• Comparative analysis of transcriptional and epigenetic landscapes.
• Assessment of S-specific memory CD4 T cells from individuals exposed to SARS-CoV-2 via infection or mRNA vaccination.
• In vitro proliferation assays.

Main Results:

• Nearly 2 years post-priming, infection-induced memory CD4 T cells showed enrichment for cytotoxicity and interferon-stimulated genes, linked to altered chromatin accessibility.
• Infection-primed CD4 T cells exhibited reduced in vitro proliferative capacity compared to vaccine-primed cells.
• Booster immunization and breakthrough infections minimally altered the transcriptional state of S-specific memory CD4 T cells.

Conclusions:

• Inflammation associated with SARS-CoV-2 infection durably imprints CD4 T cell memory.
• This imprinting affects CD4 T cell function and may have implications for long-term immunity.
• The functional state of memory CD4 T cells is established early and is resistant to subsequent immune challenges.