Back to Search
Start Over
Characterization of antigen-specific CD8+ memory T cell subsets in peripheral blood of patients with multiple sclerosis.
- Source :
-
Frontiers in immunology [Front Immunol] 2023 May 04; Vol. 14, pp. 1110672. Date of Electronic Publication: 2023 May 04 (Print Publication: 2023). - Publication Year :
- 2023
-
Abstract
- Background: Increasing evidence indicates the importance of CD8 <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br />Methods: The myelin oligodendrocyte glycoprotein (MOG)-specific CD8 <superscript>+</superscript> 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.<br />Results: We found that MS patients had elevated frequency of MOG-specific CD8 <superscript>+</superscript> T cells, MOG-specific central memory T cells (T <subscript>CM</subscript> ), MOG-specific CD8 <superscript>+</superscript> effector memory T cells (T <subscript>EM</subscript> ), and MOG-specific CD8 <superscript>+</superscript> terminally differentiated cells (T <subscript>EMRA</subscript> ); elevated granzyme B expression on MOG-specific CD8 <superscript>+</superscript> T <subscript>CM</subscript> ; and, on MOG-specific CD8 <superscript>+</superscript> T <subscript>EM</subscript> , 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 <superscript>+</superscript> T <subscript>CM</subscript> , granzyme B expression in CD8 <superscript>+</superscript> T <subscript>CM</subscript> , and granzyme B and perforin expression on CD8 <superscript>+</superscript> T <subscript>EM</subscript> , but with reduced PD-1 expression on CD8 <superscript>+</superscript> T <subscript>EM</subscript> .<br />Conclusion: The dysregulation of antigen-specific CD8 <superscript>+</superscript> 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.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2023 Liu, Yang, Fan, Yuan, Ma, Wang, Lu, Yuan, Zou, Zhang and Liu.)
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 37215118
- Full Text :
- https://doi.org/10.3389/fimmu.2023.1110672