Abstract

As a prevalent autoimmune disease of the central nervous system in young adults, multiple sclerosis (MS) is mediated by T cells, particularly CD4+ subsets. Given the evidence that the perturbation in reactive oxygen species (ROS) production has a pivotal role in the onset and progression of MS, its regulation through the antioxidant molecules is too important. Here, we investigated the level of the redox system components in lymphocytes and CD4+ T cells of MS patients. The study was performed on relapsing-remitting MS (RRMS) patients (n = 29) and age- and sex-matched healthy controls (n = 15). Peripheral blood mononuclear cells (PBMCs) were cultured and stimulated by anti-CD3/CD28. The level of ROS, anion superoxide (O2−), and L-𝛾-glutamyl-Lcysteinylglycine (GSH) was measured by flow cytometry in lymphocytes/CD4+ T cells. The gene expression level of gp91phox, catalase, superoxide dismutase 1/2 (SOD), and nuclear factor-E2-related factor (Nrf2) was also measured by real-time PCR. We found that lymphocytes/CD4+ T cells of RRMS patients at the relapse phase significantly produced higher levels of ROS and O2− compared to patients at the remission phase (P value < 0.001) and healthy controls (P value < 0.001 and P value < 0.05, respectively). Interestingly, the gene expression level of gp91phox, known as the catalytic subunit of the NADPH oxidase, significantly increased in MS patients at the relapse phase (P value < 0.05). Furthermore, the catalase expression augmented in patients at the acute phase (P value < 0.05), while an increased expression of SOD1 and Nrf2 was found in RRMS patients at relapse and remission phases (P value < 0.05). The increased production of ROS in CD4+ T cells of RRMS patients highlights the importance of amplifying antioxidant components as an efficient approach to ameliorate disease activity in MS patients.

Highlights

  • Multiple sclerosis (MS) is an inflammatory and immunemediated disease of the central nervous system (CNS) common in young adults [1]

  • For evaluation of the reactive oxygen species (ROS) and antioxidant levels in lymphocytes/CD4+ T cells of MS patients, 29 relapsing-remitting MS (RRMS) patients at relapse and remission phases and 15 healthy controls were examined in the current study (Table 2)

  • ROS/Superoxide and GSH Production Increased in CD4+ T Cells of RRMS Patients

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Summary

Introduction

Multiple sclerosis (MS) is an inflammatory and immunemediated disease of the central nervous system (CNS) common in young adults [1]. Whereas MS prevalence has an increasing trend in the world, disease prevention and management could reduce its socioeconomic impact [2]. Together with environmental stimuli, play a substantial role in MS susceptibility [1]. Numerous studies pointed to the central role of CD4+ T cell populations in the disease pathogenesis. Following the recognition of myelin-like peptides, circulating CD4+ T cells infiltrate into the CNS, leading to demyelination through various effector molecules [3, 4]. A growing body of evidence speculated the involvement of oxidative stress in the initiation and progression of many autoimmune diseases, including MS [5, 6]

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