TNF MAIT细胞的转录形状与SARS-CoV-2疫苗接种后的B细胞反应有关
Paolo Marzano1, Simone Balin1, Sara Terzoli2,3
1Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Frontiers in immunology
|August 11, 2023
概括
粘膜相关不变T细胞 (MAIT) 是一种免疫细胞,在SARS-CoV-2疫苗接种后产生TNF,促进B细胞激活和抗体产生. 这表明MAIT细胞可以在未来的mRNA疫苗中用作辅助剂.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 细胞生物学 细胞生物学
背景情况:
- 粘膜相关的不变T细胞 (MAIT) 参与了对mRNA疫苗的适应性免疫反应.
- 连接MAIT细胞与疫苗反应,特别是B细胞激活的确切机制尚不清楚.
- 了解这些相互作用对于优化疫苗疗效和开发新型疫苗策略至关重要.
研究的目的:
- 研究MAIT细胞在接种SARS-CoV-2mRNA (BNT162b2) 疫苗后的适应性免疫反应中的作用.
- 阐明有关MAIT细胞反应,特别是TNF产生如何影响接种疫苗后B细胞激活的机制性见解.
- 探索MAIT细胞在基于mRNA的疫苗平台中作为细胞辅助剂的潜力.
主要方法:
- 纵向单细胞RNA测序 (scRNA-seq) 和单细胞T细胞受体测序 (scTCR-seq) 在接受两剂BNT162b2 mRNA疫苗的健康成年人的外周血液单核细胞 (PBMC) 上进行.
- 在多个时间点收集PBMC:疫苗接种前,疫苗接种后3天和17天,以及疫苗接种后3天和3个月.
- 计算方法,包括功能通路丰富 (Reactome),效应细胞偏振动力学 (RNA Velocity,CellRank) 和细胞间通信分析 (NicheNet),用于分析scRNA/TCR-seq数据.
主要成果:
- 在BNT162b2重复接种疫苗后,MAIT细胞被确定为瘤坏死因子 (TNF) 的重要来源,在第二剂疫苗接种后诱导了TNF特征.
- MAIT细胞增加TNF表达与MAIT细胞增殖相关,并增强了抗SARS-CoV-2抗体的产生.
- 分析揭示了MAIT细胞和B细胞子集之间的预测TNF介导相互作用,特别是针对常规切换记忆B细胞,这对长期免疫至关重要.
结论:
- 接种SARS-CoV-2 BNT162b2疫苗可以调节MAIT细胞频率和效应因子,从而可能增强B细胞激活和抗体反应.
- 这项研究强调了产生TNF的MAIT细胞在对mRNA疫苗接种的适应性免疫反应中的重要作用.
- MAIT细胞显示出作为未来基于mRNA的疫苗开发的细胞辅助剂的前景.
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