Analysis of T cell and natural killer cell characteristics in cerebrospinal fluid of multiple sclerosis patients based on single-cell transcriptome sequencing
10.3760/cma.j.cn113694-20250320-00149
- VernacularTitle:基于单细胞转录组测序分析多发性硬化患者脑脊液中T细胞及自然杀伤细胞特征
- Author:
Xue YANG
1
;
Fanju LI
;
Zhenzhen HU
;
Jingtian ZHE
;
Zhimian ZHANG
;
Manxia WANG
;
Xiaoling LI
Author Information
1. 兰州大学第二医院神经内科，兰州730030
- Publication Type:Journal Article
- Keywords:
Multiple sclerosis;
T-lymphocytes;
Killer cells, natural;
CD4-positive T-lymphocytes;
CD8-positive T-lymphocytes;
Cerebrospinal fluid
- From:
Chinese Journal of Neurology
2025;58(7):757-767
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the characteristics of T cells and natural killer (NK) cells in cerebrospinal fluid of patients with multiple sclerosis (MS).Methods:Cerebrospinal fluids from patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls attending the Second Hospital of Lanzhou University from January 2023 to October 2024 were collected and analyzed by single-cell RNA sequencing (scRNA-seq) and flow cytometry, and T and NK cell characteristics were summarized and compared in the two groups. The proposed time-series analysis was used to explore the differentiation trajectories of T cells and NK cells.Results:A total of 3 patients with RRMS and 3 healthy controls underwent scRNA-seq, and 6 patients with RRMS and 4 healthy controls underwent flow cytometry. The composition of cerebrospinal fluid T and NK cell subtypes was similar in the RRMS group and the healthy control group, but the proportion of the cell subtypes differed. The RRMS group exhibited significantly higher frequencies of CD4 +Naive T- IL7R [1 529/9 055(16.89%) vs 1 423/9 910(14.36%), χ2=22.980, P<0.001], CD4 +Naive T- CCR7 [1 573/9 055(17.37%) vs 948/9 910(9.57%), χ2=250.114, P<0.001], and CD4 +Naive T- LTB [1 369/9 055(15.12%) vs 1 079/9 910(10.89%), χ2=75.336, P<0.001] subsets compared to controls. Conversely, the control group demonstrated greater proportions of CD4 +Th1- GZMA [1 255/9 910(12.66%) vs 719/9 055(7.94%), χ2=113.213, P<0.001] and CD8 +Tem- GZMK cells [1 607/9 910(16.22%) vs 1 232/9 055(13.61%), χ2=25.326, P<0.001] than the RRMS group. The transcription factors and gene expression of each T cell subtype were also different between the 2 groups, and CD4 initial T cells and CD8 effector T cells were located at the beginning and the end of the differentiation trajectory, respectively. Conclusions:The cerebrospinal fluid of MS patients is characterized by increased expression of genes involved in T cell differentiation and over-activation of immune cells.
