{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:19:43Z","timestamp":1792685983734,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870951, 82071342"],"award-info":[{"award-number":["81870951, 82071342"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Increasing evidence indicates the importance of CD8<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The myelin oligodendrocyte glycoprotein (MOG)-specific CD8<jats:sup>+<\/jats:sup> memory T cell subsets and their related cytokines (perforin, granzyme B, interferon (IFN)-\u03b3) 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that MS patients had elevated frequency of MOG-specific CD8<jats:sup>+<\/jats:sup> T cells, MOG-specific central memory T cells (T<jats:sub>CM<\/jats:sub>), MOG-specific CD8<jats:sup>+<\/jats:sup> effector memory T cells (T<jats:sub>EM<\/jats:sub>), and MOG-specific CD8<jats:sup>+<\/jats:sup> terminally differentiated cells (T<jats:sub>EMRA<\/jats:sub>); elevated granzyme B expression on MOG-specific CD8<jats:sup>+<\/jats:sup> T<jats:sub>CM<\/jats:sub>; and, on MOG-specific CD8<jats:sup>+<\/jats:sup> T<jats:sub>EM<\/jats:sub>, 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<jats:sup>+<\/jats:sup> T<jats:sub>CM<\/jats:sub>, granzyme B expression in CD8<jats:sup>+<\/jats:sup> T<jats:sub>CM<\/jats:sub>, and granzyme B and perforin expression on CD8<jats:sup>+<\/jats:sup> T<jats:sub>EM<\/jats:sub>, but with reduced PD-1 expression on CD8<jats:sup>+<\/jats:sup> T<jats:sub>EM<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The dysregulation of antigen-specific CD8<jats:sup>+<\/jats:sup> 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 <jats:italic>via<\/jats:italic> 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 <jats:italic>via<\/jats:italic> the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1110672","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T04:36:16Z","timestamp":1683174976000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Characterization of antigen-specific CD8+ memory T cell subsets in peripheral blood of patients with multiple 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