4.6 Article

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

Journal

Publisher

WILEY
DOI: 10.1002/acn3.51241

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Funding

  1. National Key Research and Development Program of China [2017YFC0907704]
  2. Sichuan Cancer Hospital & Institute Tumor Immunological Program [YBR2009002]
  3. Department of science and Technology of Sichuan Province [2018SZ0388, 2020YFS0219]

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The study found that circulating CD8(+) T cell subpopulations were significantly altered in NMOSD and MS patients. Patients treated with immunotherapy showed improvements in CD8(+) T cell subpopulations in NMOSD. Furthermore, NMOSD patients exhibited higher levels of pro-inflammatory cytokines compared to healthy controls and MS patients, but these levels decreased in NMOSD patients receiving immunotherapy.
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 naive (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 gamma and TNF alpha) 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 gamma(+)CD8(+) T cells and proportions of TNF alpha(+)CD8(+) T cells than HC and MS cohorts. On the contrary, obviously decreased IFN gamma and TNF alpha 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.

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