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单细胞测序鉴定灭活 SARS-CoV-2 疫苗接种后 CD8 MAIT 细胞分化和基因表达上调。

Upregulated CD8 MAIT cell differentiation and gene expression after inactivated SARS-CoV-2 vaccination identified by single-cell sequencing.

机构信息

Medical Laboratory of the Third Affiliated Hospital of Shenzhen University, Shenzhen, China.

Department of Critical Care Medicine, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China.

出版信息

Front Immunol. 2023 Aug 15;14:1174406. doi: 10.3389/fimmu.2023.1174406. eCollection 2023.

Abstract

BACKGROUND

The primary strategy for reducing the incidence of COVID-19 is SARS-CoV-2 vaccination. Few studies have explored T cell subset differentiation and gene expressions induced by SARS-CoV-2 vaccines. Our study aimed to analyze T cell dynamics and transcriptome gene expression after inoculation with an inactivated SARS-CoV-2 vaccine by using single-cell sequencing.

METHODS

Single-cell sequencing was performed after peripheral blood mononuclear cells were extracted from three participants at four time points during the inactivated SARS-CoV-2 vaccination process. After library preparation, raw read data analysis, quality control, dimension reduction and clustering, single-cell T cell receptor (TCR) sequencing, TCR V(D)J sequencing, cell differentiation trajectory inference, differentially expressed genes, and pathway enrichment were analyzed to explore the characteristics and mechanisms of postvaccination immunodynamics.

RESULTS

Inactivated SARS-CoV-2 vaccination promoted T cell proliferation, TCR clone amplification, and TCR diversity. The proliferation and differentiation of CD8 mucosal-associated invariant T (MAIT) cells were significantly upregulated, as were gene expression and the two pathways of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay, and translational initiation.

CONCLUSION

Upregulation of CD8 MAIT cell differentiation and expression after inactivated SARS-CoV-2 vaccination was demonstrated by single-cell sequencing. We conclude that the inactivated SARS-CoV-2 vaccine elicits adaptive T cell immunity to enhance early immunity and rapid response to the targeted virus.

摘要

背景

降低 COVID-19 发病率的主要策略是接种 SARS-CoV-2 疫苗。很少有研究探讨 SARS-CoV-2 疫苗诱导的 T 细胞亚群分化和基因表达。我们的研究旨在通过单细胞测序分析接种灭活 SARS-CoV-2 疫苗后 T 细胞的动态和转录组基因表达。

方法

在灭活 SARS-CoV-2 疫苗接种过程中,从三名参与者的四个时间点提取外周血单核细胞,进行单细胞测序。在文库制备、原始读数据分析、质量控制、降维和聚类、单细胞 T 细胞受体 (TCR) 测序、TCR V(D)J 测序、细胞分化轨迹推断、差异表达基因和通路富集分析后,探讨接种后免疫动力学的特征和机制。

结果

灭活 SARS-CoV-2 疫苗促进了 T 细胞增殖、TCR 克隆扩增和 TCR 多样性。CD8 黏膜相关不变 T (MAIT) 细胞的增殖和分化显著上调,基因表达和核转录 mRNA 分解代谢过程、无意义介导的衰变和翻译起始的两个途径也上调。

结论

通过单细胞测序证明,灭活 SARS-CoV-2 疫苗接种后 CD8 MAIT 细胞分化和 表达上调。我们得出结论,灭活 SARS-CoV-2 疫苗引发适应性 T 细胞免疫,增强早期免疫和对靶向病毒的快速反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272b/10466403/be1f4541dbf0/fimmu-14-1174406-g001.jpg

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