Dataset Information

CD8⁺ T cell subpopulations and pro-inflammatory cytokines in neuromyelitis optica spectrum disorder.

ABSTRACT:

Objective

Our study aimed to investigate circulating CD8⁺ T cell subpopulations and pro-inflammatory cytokines in the neuromyelitis optica spectrum disorder (NMOSD).

Methods

A total of 121 peripheral blood samples were obtained from 57 patients with NMOSD, 34 patients with multiple sclerosis (MS), and 30 sex- and age-matched healthy controls (HCs) for detection of CD8⁺ T cell subpopulations, including phenotypes of naïve (T_N , CD62L^hi CD45RO^- ), effector/memory (T_E/M , CD62L^lo CD45RO⁺ ), memory precursor (T_MP , CD127^hi KLRG1^lo ), and short lived effector (T_SLEC , CD127^lo KLRG1^hi ). In addition, 36 samples from 18 NMOSD, 12 MS, and 6 sex- and age-matched HCs for detecting pro-inflammatory cytokines (IFN? and TNF?) using flow cytometry.

Results

Compared with HCs, we found significantly reduced CD8⁺ T_N and increased CD8⁺ T_E/M in both NMOSD and MS?while decreased CD8⁺ T_MP was only observed in NMOSD. Patients treated with immunotherapy were associated with increased CD8⁺ T_N and decreased CD8⁺ T_E/M in NMOSD. Moreover NMOSD cohort showed significant higher proportions of IFN?⁺ CD8⁺ T cells and proportions of TNF?⁺ CD8⁺ T cells than HC and MS cohorts. On the contrary, obviously decreased IFN? and TNF? were found in NMOSD patients treated with immunotherapy. Furthermore, Multivariate linear regression analyses revealed that age was negatively correlated with CD8⁺ T_N and T_MP , and positively associated with T_SLEC ; however, sex, EDSS scores and disease phase were not significantly associated with CD8⁺ T subpopulations.

Interpretation

This current study provides an evidence that circulating CD8⁺ T cell with abnormal subpopulations and increased pro-inflammatory were associated with pathogenesis of autoimmune demyelinating disease of CNS, especially in NMOSD.

SUBMITTER: Shi Z

PROVIDER: S-EPMC7818084 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

CD8<sup>+</sup> T cell subpopulations and pro-inflammatory cytokines in neuromyelitis optica spectrum disorder.

Shi Ziyan Z Qiu Yuhan Y Zhao Zhengyang Z Wen Dingke D Chen Hongxi H Du Qin Q Zhang Ying Y Wang Jiancheng J Yan Chao C Yang Mu M Yang Mu M Zhou Hongyu H

Annals of clinical and translational neurology 20201124 1

<h4>Objective</h4>Our study aimed to investigate circulating CD8<sup>+</sup> T cell subpopulations and pro-inflammatory cytokines in the neuromyelitis optica spectrum disorder (NMOSD).<h4>Methods</h4>A total of 121 peripheral blood samples were obtained from 57 patients with NMOSD, 34 patients with multiple sclerosis (MS), and 30 sex- and age-matched healthy controls (HCs) for detection of CD8<sup>+</sup> T cell subpopulations, including phenotypes of naïve (T<sub>N</sub> , CD62L<sup>hi</sup> CD ...[more]

PMID: 33231379

Similar Datasets

Project description:BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system. Although complement-dependent astrocyte damage mediated by anti-aquaporin 4 autoantibody (AQP4-Ab) is well acknowledged to be the core of NMOSD pathogenesis, additional inflammatory cascades may contribute to the establishment of lesion formation. Thus, in this study, we investigated the possible pathogenic role of immune-reactive mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) of NMOSD patients.MethodsUsing quantitative polymerase chain reaction, we measured extracellular mtDNA levels in CSF of NMOSD patients positive for AQP4-Ab. Patients with multiple sclerosis or other neurological diseases were examined as controls. Pre- and post-treatment extracellular mtDNA levels were also compared in the NMOSD group. Extracellular mtDNA release from human astrocytes was analyzed in vitro utilizing NMOSD sera, and interleukin (IL)-1? production was measured in supernatants of mixed glial cells stimulated with DNA fraction of CSF derived from NMOSD patients. Furthermore, specific innate immune pathways mediating the IL-1? production by mtDNA were investigated in peripheral blood mononuclear cells with selective inhibitors of Toll-like receptor 9 (TLR9) and NOD-like receptor protein 3 (NLRP3) inflammasomes.ResultsExtracellular mtDNA level was specifically elevated in acute phase of NMOSD CSF. In vitro studies provided the evidence that mtDNA is released from human astrocytes by NMOSD sera. In addition, DNA fraction isolated from NMOSD CSF promoted secretion of IL-1? from mixed glial cells. Selective inhibition of TLR9 and NLRP3 inflammasomes revealed that mtDNA-mediated IL-1? production depends on specific innate immune pathways.ConclusionExtracellular mtDNA is specifically elevated in the CSF of patients with acute phase NMOSD, and mtDNA released by AQP4-Ab-mediated cellular damage elicits the innate immune cascades via TLR9 and NLRP3 inflammasomes pathways. Our study highlights mtDNA-mediated innate immune pathways as a novel therapeutic target for future treatment of NMOSD patients.