{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:46:53Z","timestamp":1792698413002,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,12,8]],"date-time":"2009-12-08T00:00:00Z","timestamp":1260230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to investigate the role of CD8+ CD25+ FoxP3+ cells during the course of multiple sclerosis (MS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood and cerebrospinal fluid (CSF) CD8+ T\u2010cell clones (TCCs) recognizing autoreactive CD4+ T cells were isolated from 20 MS patients during exacerbations, 15 patients in remission, 15 healthy subjects, and 10 patients with other inflammatory neurological diseases. Characteristics of noncytotoxic CD8+ CD25+ regulatory T cells were studied. Cell phenotype was evaluated using flow cytometry. Cytokine production and phospho\u2010signal transducer and activator of transcription 3 (STAT3) concentration were determined using enzyme\u2010linked immunosorbent assay. To assess 2,3\u2010dioxygenase (IDO) activity on dendritic cells (DCs), kynurenine concentration was measured by high\u2010performance liquid chromatography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inhibition of CD4+ self\u2010reactive T\u2010cell proliferation, and of interferon\u2010\u03b3 and interleukin (IL)\u201017 secretion, was observed after adding CD8+ CD25+ FoxP3+ cells to cultures. Suppression was abrogated by silencing FoxP3 using small interfering RNA. Cells were CD122+, CTLA\u20104+, GITR+, CCR7+, and CD62L+, producing IL\u201010 and transforming growth factor\u2010\u03b2. CD8+ CD25+ FoxP3+ cells downregulated costimulatory molecule expression on dendritic cells through a STAT3\u2010mediated pathway, resulting in less efficient antigen presentation, and induced IDO expression on DCs through STAT3 and cytotoxic T\u2010lymphocyte antigen 4\u2010dependent mechanisms. CD8+ regulatory TCC cloning frequency studied in blood and CSF was suppressed to a greater degree during exacerbations than during remission or in controls. Likewise, in CSF of MS patients during acute exacerbations, lower levels of CD8+ CD25+ FoxP3+ T cells were detected using flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>CD8+ CD25+ FoxP3+ cells are novel regulatory cells exerting significant influence over self\u2010reactive CD4+ T\u2010cell regulation during the course of MS. Induction of these cells may provide new therapeutic alternatives for MS by eliminating or inhibiting self\u2010reactive T cells. 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