CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph nodes and blood following mRNA vaccination in humans

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mRNA vaccination induce robust CD4+ T cell responses. Using single-cell transcriptomics, here, we evaluated CD4+ T cells specific for the SARS-CoV-2 spike protein in the blood and draining lymph nodes (dLNs) of individuals 3 months and 6 months after vaccination with the BNT162b2 mRNA vaccine. We analyzed 1,277 spike-specific CD4+ T cells, including 238 defined using Trex, a deep learning-based reverse epitope mapping method to predict antigen specificity. Human dLN spike-specific CD4+ follicular helper T (TFH) cells exhibited heterogeneous phenotypes, including germinal center CD4+ TFH cells and CD4+IL-10+ TFH cells. Analysis of an independent cohort of SARS-CoV-2-infected individuals 3 months and 6 months after infection found spike-specific CD4+ T cell profiles in blood that were distinct from those detected in blood 3 months and 6 months after BNT162b2 vaccination. Our findings provide an atlas of human spike-specific CD4+ T cell transcriptional phenotypes in the dLNs and blood following SARS-CoV-2 vaccination or infection. Peripheral blood and/or drainging lymph node immune cells were across time points for infected or vaccinated individuals underwent single-cell RNA and T cell receptor sequencing to analyze the adaptive immune response.

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染与mRNA疫苗接种均可诱导强烈的CD4+ T细胞应答。本研究借助单细胞转录组学技术，对接种BNT162b2 mRNA疫苗后3个月及6个月的个体血液与引流淋巴结（draining lymph nodes, dLNs）中针对SARS-CoV-2刺突蛋白的CD4+ T细胞进行了评估分析；共纳入1277株刺突蛋白特异性CD4+ T细胞，其中238株通过基于深度学习的反向表位作图方法Trex完成抗原特异性预测与鉴定。人引流淋巴结内的刺突蛋白特异性CD4+滤泡辅助T（follicular helper T, TFH）细胞呈现异质性表型，涵盖生发中心CD4+ TFH细胞与CD4+IL-10+ TFH细胞两类亚群。对感染后3个月及6个月的SARS-CoV-2感染个体组成的独立队列开展分析后发现，其血液中的刺突蛋白特异性CD4+ T细胞特征与BNT162b2疫苗接种后3、6个月个体血液中的检测结果存在显著差异。本研究结果构建了SARS-CoV-2感染或mRNA疫苗接种后，个体引流淋巴结与血液中刺突蛋白特异性CD4+ T细胞的转录表型图谱；并对感染或疫苗接种个体在多个时间点采集的外周血及/或引流淋巴结免疫细胞开展了单细胞RNA测序与T细胞受体测序，以解析适应性免疫应答。