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 (IFNγ and TNFα) 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 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⁺ 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.