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

Ann Clin Transl Neurol. 2021 Jan;8(1):43-53. doi: 10.1002/acn3.51241. Epub 2020 Nov 24.

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 (TN , CD62Lhi CD45RO- ), effector/memory (TE/M , CD62Llo CD45RO+ ), memory precursor (TMP , CD127hi KLRG1lo ), and short lived effector (TSLEC , CD127lo KLRG1hi ). In addition, 36 samples from 18 NMOSD, 12 MS, and 6 sex- and age-matched HCs for detecting pro-inflammatory cytokines (IFNγ and TNFα) using flow cytometry.

Results: Compared with HCs, we found significantly reduced CD8+ TN and increased CD8+ TE/M in both NMOSD and MS,while decreased CD8+ TMP was only observed in NMOSD. Patients treated with immunotherapy were associated with increased CD8+ TN and decreased CD8+ TE/M in NMOSD. Moreover NMOSD cohort showed significant higher proportions of IFNγ+ CD8+ T cells and proportions of TNFα+ CD8+ T cells than HC and MS cohorts. On the contrary, obviously decreased IFNγ and TNFα were found in NMOSD patients treated with immunotherapy. Furthermore, Multivariate linear regression analyses revealed that age was negatively correlated with CD8+ TN and TMP , and positively associated with TSLEC ; 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • Cohort Studies
  • Cytokines / immunology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuromyelitis Optica / immunology*
  • T-Lymphocyte Subsets / immunology*

Substances

  • Cytokines

Grant support

This work was funded by National Key Research and Development Program of China grant 2017YFC0907704; Sichuan Cancer Hospital & Institute Tumor Immunological Program grant YBR2009002; Department of Science and Technology of Sichuan Province grants 2018SZ0388 and 2020YFS0219.