Characterization of antigen-specific CD8+ memory T cell subsets in peripheral blood of patients with multiple sclerosis

• Published in: Frontiers in immunology 2023-05, Vol.14, p.1110672-1110672
• Main Authors: Liu, Pen-Ju, Yang, Ting-Ting, Fan, Ze-Xin, Yuan, Guo-Bin, Ma, Lin, Wang, Ze-Yi, Lu, Jian-Feng, Yuan, Bo-Yi, Zou, Wen-Long, Zhang, Xing-Hu, Liu, Guang-Zhi
• Format: Article
• Language: English
• Subjects: CD8-Positive T-Lymphocytes; Cytokines; Granzymes; Humans; Immunology; Memory T Cells; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; oligodendrocyte glycoprotein; pentamer; Perforin; peripheral blood mononuclear cells; Programmed Cell Death 1 Receptor
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1110672

Increasing evidence indicates the importance of CD8 T cells in autoimmune attack against CNS myelin and axon in multiple sclerosis (MS). Previous research has also discovered that myelin-reactive T cells have memory phenotype functions in MS patients. However, limited evidence is available regarding the role of CD8 memory T cell subsets in MS. This study aimed to explore potential antigen-specific memory T cell-related biomarkers and their association with disease activity. The myelin oligodendrocyte glycoprotein (MOG)-specific CD8 memory T cell subsets and their related cytokines (perforin, granzyme B, interferon (IFN)-γ) and negative co-stimulatory molecules (programmed cell death protein 1 (PD-1), T- cell Ig and mucin domain 3 (Tim-3)) were analyzed by flow cytometry and real-time PCR in peripheral blood of patients with relapsing-remitting MS. We found that MS patients had elevated frequency of MOG-specific CD8 T cells, MOG-specific central memory T cells (T ), MOG-specific CD8 effector memory T cells (T ), and MOG-specific CD8 terminally differentiated cells (T ); elevated granzyme B expression on MOG-specific CD8 T ; and, on MOG-specific CD8 T , elevated granzyme B and reduced PD-1 expression. The Expanded Disability Status Scale score (EDSS) in MS patients was correlated with the frequency of MOG-specific CD8 T , granzyme B expression in CD8 T , and granzyme B and perforin expression on CD8 T , but with reduced PD-1 expression on CD8 T . The dysregulation of antigen-specific CD8 memory T cell subsets, along with the abnormal expression of their related cytokines and negative co-stimulatory molecules, may reflect an excessive or persistent inflammatory response induced during early stages of the illness. Our findings strongly suggest positive regulatory roles for memory T cell populations in MS pathogenesis, probably molecular mimicry to trigger or promote abnormal peripheral immune responses. Furthermore, downregulated PD-1 expression may stimulate a positive feedback effect, promoting MS-related inflammatory responses the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS.