Department of Laboratory Medicine, Shenzhen Third People's Hospital, and Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, and Affiliated Hospital, Guangdong Medical University, Shenzhen, Guangdong, China.
Division of Research, Institute of Tuberculosis, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, China.
Scand J Immunol. 2020 Apr;91(4):e12858. doi: 10.1111/sji.12858. Epub 2020 Jan 8.
To understand functional role of PD-1-expressing MAIT cells during tuberculosis infection in humans, sorted PD-1 and PD-1 MAIT cells from pleural effusions of patients with pleural tuberculosis were subjected to transcriptome sequencing. PD-1-expressing MAIT cells were analysed by flow cytometry and their phenotypic and functional features were investigated. Transcriptome sequencing identified 144 genes that were differentially expressed between PD-1 and PD-1 MAIT cells from tuberculous pleural effusions and CXCL13 was the gene with highest fold difference. The level of PD-1-expressing MAIT cells was associated with extent of TB infection in humans. PD-1-expressing MAIT cells had increased production of CXCL13 and IL-21 as determined by flow cytometry. PD-1 CXCR5 MAIT cells were significantly expanded in pleural effusions from patients with pleural tuberculosis as compared with those from peripheral blood of both patients with tuberculosis and healthy controls. Although PD-1 CXCR5 MAIT cells from tuberculous pleural effusions had reduced IFN-γ level and increased expression of Tim-3 and GITR, they showed activated phenotype and had higher glucose uptake and lipid content. It is concluded that PD-1-expressing MAIT cells had reduced IFN-γ level but increased production of both CXCL13 and IL-21.
为了了解 PD-1 表达的 MAIT 细胞在人类结核感染中的功能作用，我们从结核性胸腔积液患者的胸腔积液中分离出 PD-1 和 PD-1 MAIT 细胞，并进行了转录组测序。通过流式细胞术分析 PD-1 表达的 MAIT 细胞，并研究其表型和功能特征。转录组测序鉴定出 144 个在结核性胸腔积液中 PD-1 和 PD-1 MAIT 细胞之间差异表达的基因，其中 CXCL13 是差异倍数最高的基因。PD-1 表达的 MAIT 细胞的水平与人类 TB 感染的程度相关。通过流式细胞术确定，PD-1 表达的 MAIT 细胞增加了 CXCL13 和 IL-21 的产生。与结核患者外周血和健康对照者相比，来自结核性胸腔积液的 PD-1 CXCR5 MAIT 细胞显著扩增。尽管来自结核性胸腔积液的 PD-1 CXCR5 MAIT 细胞的 IFN-γ 水平降低，Tim-3 和 GITR 的表达增加，但它们表现出激活的表型，并且具有更高的葡萄糖摄取和脂质含量。结论是，PD-1 表达的 MAIT 细胞的 IFN-γ 水平降低，但 CXCL13 和 IL-21 的产生增加。
