{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:54:46Z","timestamp":1781636086149,"version":"3.54.5"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Autoreactive T-cells against myelin are implicated in multiple sclerosis (MS) however, the functional relevance of IL2-producing central memory T-cells and IFN\u0263-producing effector T-cells have not been assessed. In this study we aimed to t investigate association of IL2\u2009+\u2009and IFN\u03b3\u2009+\u2009myelin reactive memory T-cells with MS severity and progression. Thirty relapsing\u2013remitting MS (RRMS) patients and 32 age-matched healthy subjects (HS) were analyzed. Peripheral Blood Mononuclear Cells (PBMC) responses to proteolipid protein (PLP), myelin basic protein (MBP), and myelin oligodendrocyte glycoprotein (MOG) were assessed using IFN\u03b3\/IL2-FluoroSpot assay and correlated with disease severity and progression. Flow cytometry was performed to characterize central (CD45RO+CD62L+) and effector memory (CD45RO+CD62L-) T-cell subsets. Patients showed increased frequency and magnitude of IL2 responses to PLP compared with HS. Higher PLP-induced IL2 responses were in correlation with clinical severity of the last occurring relapse, including EDSS, EDSS change, and longer time from last occurring relapse (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Odds ratios\u00a0(OR) confirmed associations between IL2-responses and last occurring relapse severity (OR range 5.3\u201322.5). Flow cytometry confirmed increase of central memory CD4\u2009+\u2009and CD8\u2009+\u2009T-cells in RRMS, whereas effector memory frequencies were unchanged. In RRMS, circulating PLP-reactive IL2\u2009+\u2009central memory T-cells are linked to severity of last occurring relapse, representing an immunological imprint of recent disease activity rather than cumulative burden.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-39859-9","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:45:09Z","timestamp":1771051509000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myelin-specific IL2\u2009+\u2009T-cells are associated with last occurring relapse severity in relapsing\u2013remitting multiple sclerosis"],"prefix":"10.1038","volume":"16","author":[{"given":"Rina","family":"Zilkha-Falb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tali","family":"Drori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katya","family":"Shwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gurevich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"39859_CR1","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1136\/jnnp.2004.045518","volume":"76","author":"A Achiron","year":"2005","unstructured":"Achiron, A. et al. Cognitive patterns and progression in multiple sclerosis: construction and validation of percentile curves. J. Neurol. Neurosurg. Psychiatry. 76, 744\u2013749 (2005).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"39859_CR2","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.nic.2008.09.002","volume":"18","author":"C Confavreux","year":"2008","unstructured":"Confavreux, C. & Vukusic, S. The clinical epidemiology of multiple sclerosis. Neuroimaging Clin. N Am. 18, 589\u2013622 (2008). ix-x.","journal-title":"Neuroimaging Clin. N Am."},{"key":"39859_CR3","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1002\/1097-4547(20010201)63:3<290::AID-JNR1023>3.0.CO;2-4","volume":"63","author":"N Hellings","year":"2001","unstructured":"Hellings, N. et al. T-cell reactivity to multiple Myelin antigens in multiple sclerosis patients and healthy controls. J. Neurosci. Res. 63, 290\u2013302 (2001).","journal-title":"J. Neurosci. 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SMC-7904-20) on 12.04.2023. All participants provided written informed consent prior to participating.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}],"article-number":"9011"}}