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.
摘要：
记忆CD4T细胞对人体免疫至关重要，然而，目前尚不清楚记忆形成过程中的病毒性炎症是否具有长期后果。这里,我们比较了Spike(S)特异性记忆CD4T细胞的转录和表观遗传特征,这些个体首次暴露于S是通过SARS-CoV-2感染或mRNA疫苗接种.记忆形成近2年后，通过感染建立的S特异性CD4T细胞仍然富集了与细胞毒性相关的转录本和干扰素刺激的基因，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CD4T细胞在体外的增殖能力降低。此外，S特异性记忆CD4T细胞的转录状态在加强免疫和/或突破性感染时发生了最小程度的改变.因此，感染相关的炎症持久印记CD4T细胞记忆，这会影响这些细胞的功能，并可能对长期免疫产生影响。
