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.

中文翻译：

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SARS-CoV-2 炎症持久印记记忆 CD4 T 细胞


记忆 CD4 T 细胞对人类免疫至关重要，但尚不清楚记忆形成过程中的病毒炎症是否会产生长期后果。在这里，我们比较了 24 名个体中 Spike (S) 特异性记忆 CD4 T 细胞的转录和表观遗传景观，这些人首次接触 S 是通过 SARS-CoV-2 感染或 mRNA 疫苗接种。记忆形成后近两年，通过感染建立的 S 特异性 CD4 T 细胞仍然富含与细胞毒性相关的转录物和干扰素刺激的基因，这可能是因为炎症改变了染色质可及性景观。此外，与疫苗引发的细胞相比，感染引发的 S 特异性 CD4 T 细胞在体外的增殖能力降低。此外，加强免疫和/或突破性感染对 S 特异性记忆 CD4 T 细胞的转录状态影响极小。因此，感染相关的炎症会持久地印记 CD4 T 细胞记忆，从而影响这些细胞的功能，并可能对长期免疫产生影响。