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

Frontiers in Immunology

Immunology

Jian-Feng Lu¹  Guang-Zhi Liu¹  Pen-Ju Liu¹  Lin Ma¹  Ting-Ting Yang¹  Ze-Xin Fan¹  Ze-Yi Wang¹  Guo-Bin Yuan¹  Bo-Yi Yuan¹  Wen-Long Zou¹  Xing-Hu Zhang² 

[1] Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China;Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;

关键词: multiple sclerosis;    peripheral blood mononuclear cells;    memory T cells;    oligodendrocyte glycoprotein;    pentamer;   

DOI  :  10.3389/fimmu.2023.1110672

 received in 2022-11-29, accepted in 2023-04-24,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundIncreasing 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.MethodsThe 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.ResultsWe found that MS patients had elevated frequency of MOG-specific CD8+ T cells, MOG-specific central memory T cells (TCM), MOG-specific CD8+ effector memory T cells (TEM), and MOG-specific CD8+ terminally differentiated cells (TEMRA); elevated granzyme B expression on MOG-specific CD8+ TCM; and, on MOG-specific CD8+ TEM, 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+ TCM, granzyme B expression in CD8+ TCM, and granzyme B and perforin expression on CD8+ TEM, but with reduced PD-1 expression on CD8+ TEM.ConclusionThe 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 via 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 via the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS.

【 授权许可】

Unknown   
Copyright © 2023 Liu, Yang, Fan, Yuan, Ma, Wang, Lu, Yuan, Zou, Zhang and Liu