Single-Cell TCR Sequencing Reveals the Dynamics of T Cell Repertoire Profiling During Pneumocystis Infection.

Single-Cell TCR Sequencing Reveals the Dynamics of T Cell Repertoire Profiling During Pneumocystis Infection.
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单细胞 TCR 测序揭示肺孢子虫感染期间 T 细胞库谱分析的动态

DOI:
10.3389/fmicb.2021.637500
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发表时间:
2021
影响因子:
5.2
通讯作者:
Tong ZH
Tong ZH
中科院分区:
生物学2区
文献类型:
--
作者:
Yang HQ;Wang YS;Zhai K;Tong ZH

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T细胞应答在宿主对肺孢子虫的适应性免疫中起关键作用。然而,人类免疫缺陷病毒(HIV)阴性肺孢子虫肺炎(PCP)中T细胞免疫库的动态和多样性仍不清楚。在这项研究中,单细胞RNA和单细胞T细胞受体(TCR)测序应用于从肺孢子虫感染的小鼠肺组织中分选的细胞。结果表明,肺孢子虫感染后,克隆细胞主要由CD4+ T细胞组成,其特征是T细胞活化相关基因的高表达。与未感染的对照组相比,感染肺孢子虫的小鼠显示CD4+ T细胞中TCR多样性降低,CD8+ T细胞中TCR多样性增加。Th17细胞主要为克隆性CD4+ T细胞,具有组织驻留记忆样Th17细胞的表型。此外,肺孢子虫感染的小鼠表现出对TCRβ VDJ基因的偏倚使用。两者合计,我们的特点是转录组和TCR免疫谱的扩增T细胞克隆,这表明一个歪斜的TCR库肺孢子虫感染后。
T cell responses play critical roles in host adaptive immunity against Pneumocystis. However, the dynamics and diversity of the T cell immune repertoire in human immunodeficiency virus (HIV)-negative Pneumocystis pneumonia (PCP) remains unclear. In this study, single-cell RNA and single-cell T cell receptor (TCR) sequencing were applied to cells sorted from lung tissues of mice infected with Pneumocystis. Our findings demonstrated the clonal cells were mainly composed of CD4+ T cells in response to Pneumocystis, which were marked by highly expressed genes associated with T cell activation. Mice infected with Pneumocystis showed reduced TCR diversity in CD4+ T cells and increased diversity in CD8+ T cells compared with uninfected controls. Furthermore, Th17 cells were mostly clonal CD4+ T cells, which exhibited the phenotype of tissue-resident memory-like Th17 cells. In addition, Pneumocystis-infected mice showed biased usage of TCRβ VDJ genes. Taken together, we characterized the transcriptome and TCR immune repertoires profiles of expanded T cell clones, which demonstrate a skewed TCR repertoire after Pneumocystis infection.
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