{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:14:48Z","timestamp":1782890088696,"version":"3.54.5"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Memory CD8+ T cells are central to multiple sclerosis (MS) and undergo clonal expansion, but disease-associated states remain incompletely defined.<\/jats:p>\n                  <jats:p>By single-cell profiling of circulating memory CD8+ T cells from patients with relapsing\u2013remitting MS, healthy volunteers, and neuroinflammatory controls, we identified an MS-associated cytotoxic subset with NK-like features. These cells increase around relapse activity and belong to an oligoclonal reservoir. In an independent cohort sampled at the first clinical event, an elevated frequency of NK-like CD8+ T cells predicted an aggressive MS course two years later and was associated with a migratory\/inflammatory program. Bulk and single-cell RNA-seq confirmed the NK-like transcriptional signature, and functional assays demonstrated TCR-independent cytotoxicity. Immunostaining and spatial transcriptomics revealed enrichment of these cells in MS lesions and a spatial association with macrophages\/microglia.<\/jats:p>\n                  <jats:p>Together, our results identify a cytotoxic NK-like CD8+ T-cell subset that links peripheral inflammation to CNS lesions and may serve as an early biomarker of MS severity.<\/jats:p>","DOI":"10.1093\/brain\/awag227","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:46:10Z","timestamp":1782859570000},"source":"Crossref","is-referenced-by-count":0,"title":["Blood cytotoxic natural killer-like CD8 + CD94+ T cells migrate to the brain and predict multiple sclerosis severity"],"prefix":"10.1093","author":[{"given":"Emilie","family":"Dugast","sequence":"first","affiliation":[{"name":"Nantes Universit\u00e9, CHU de Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN , F-44000, Nantes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita","family":"Shah","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU de Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN , F-44000, Nantes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Vogel","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU de Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN , F-44000, Nantes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandine","family":"Loret","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU de Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN , F-44000, Nantes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Monvoisin","sequence":"additional","affiliation":[{"name":"MICMAC INSERM U1236 , F-35043, Rennes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-5199","authenticated-orcid":false,"given":"Alexandra","family":"Garcia","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU de Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN , F-44000, Nantes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Fourgeux","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU de Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN , F-44000, Nantes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Gourain","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU de Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN , F-44000, Nantes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9o","family":"Boussamet","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU de Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN , F-44000, Nantes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Amoriello","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence , 50121 Florence ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Beno\u00eet","family":"Le Luduec","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Nataf","sequence":"additional","affiliation":[{"name":"Bank of Tissues and Cells, Hospices Civils de Lyon, H\u00f4pital Edouard Herriot , F-69003 Lyon ,","place":["France"]},{"name":"Stem-Cell and Brain Research Institute , F-69500 Bron ,","place":["France"]},{"name":"Lyon-Est School of Medicine, University Claude Bernard Lyon 1 , F-69100 Villeurbanne ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryl\u00e8ne","family":"Jacq-Foucher","sequence":"additional","affiliation":[{"name":"CIC 1413, CHU de Nantes , F-44000, Nantes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Moyon","sequence":"additional","affiliation":[{"name":"CIC 1413, CHU 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Service de Neurologie, scl\u00e9rose en plaques, pathologies de la my\u00e9line et neuro-inflammation , F-69677 Bron ,","place":["France"]},{"name":"Universit\u00e9 de Lyon. Universit\u00e9 Claude Bernard Lyon 1 , F-69000 Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Ruet","sequence":"additional","affiliation":[{"name":"Service de Neurologie, Pathologie inflammatoire du syst\u00e8me nerveux central, CRC-SEP, CHU de Bordeaux , F-33000, Bordeaux ,","place":["France"]},{"name":"Universit\u00e9 de Bordeaux, INSERM, Neurocentre Magendie, U1215 , F-33077, Bordeaux ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Le Page","sequence":"additional","affiliation":[{"name":"CHU Pontchaillou, Centre d'Investigation Clinique 1414, INSERM , F-35033, Rennes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Labauge","sequence":"additional","affiliation":[{"name":"Service de Neurologie, CHU de Montpellier , F-34090, Montpellier ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Mathey","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nancy University Hospital , F-54035 Nancy ,","place":["France"]},{"name":"Universit\u00e9 de Lorraine, Inserm, INSPIIRE , F-54000, Nancy ,","place":["France"]},{"name":"CHRU de Nancy, Universit\u00e9 de Lorraine, Inserm, CIC 1433 EC , F-54000, Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Raposo","sequence":"additional","affiliation":[{"name":"F. 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