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While treatment made huge advances, progression remains a challenge. Eomesodermin+ Th cells are associated with cytotoxicity, neuroinflammation and disease progression in secondary progressive multiple sclerosis. We performed a prospective longitudinal study over one year to investigate the role of Eomesodermin+ T cells in multiple sclerosis progression and neurodegeneration. Patients underwent detailed clinical assessment and immunophenotyping. In a subcohort of patients, cross-sectional magnetic resonance imaging using voxel-based morphometry was performed. Frequencies of Eomesodermin+ Th cells could differentiate between patients with secondary and primary progressive multiple sclerosis and correlated with B-cells in secondary progressive multiple sclerosis. Secondary progressive patients experiencing a subjective worsening of disease activity showed higher baseline frequencies of Eomesodermin+ Th cells. Higher baseline frequencies of Eomesodermin+ Th cells predicted prospective one-year disability progression in a small group of secondary progressive patients. Conclusively, voxel-based morphometry analysis revealed pronounced infratentorial brain atrophy in a sub-cohort of patients with higher Eomesodermin+ Th frequencies. In summary, Eomesodermin+ Th cells may shape a dysregulated and proinflammatory immune milieu, driving disease progression and neurodegeneration in secondary progressive multiple sclerosis with potential as both biomarker and therapeutic target.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf415","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:00:19Z","timestamp":1761393619000},"source":"Crossref","is-referenced-by-count":1,"title":["Eomesodermin-expressing CD4 Th cells and association with multiple sclerosis progression and brain atrophy"],"prefix":"10.1093","volume":"7","author":[{"given":"Marielena","family":"Bongert","sequence":"first","affiliation":[{"name":"Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital , Bochum 44791 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emelie","family":"Sch\u00f6nauer","sequence":"additional","affiliation":[{"name":"Department of Neurology, 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,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e9on","family":"Beyer","sequence":"additional","affiliation":[{"name":"Center for Protein Diagnostics (ProDi), Biospectroscopy, Ruhr-University Bochum , Bochum 44801 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Gerwert","sequence":"additional","affiliation":[{"name":"Center for Protein Diagnostics (ProDi), Biospectroscopy, Ruhr-University Bochum , Bochum 44801 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Immunology, National Institute of Neuroscience, NCNP , Tokyo 187-8502 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Lukas","sequence":"additional","affiliation":[{"name":"Institute of Neuroradiology, Ruhr-University Bochum, St. Josef-Hospital , Bochum 44791 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5360-0419","authenticated-orcid":false,"given":"Ingo","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Ruhr-University Bochum , Bochum 44801 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0997-2725","authenticated-orcid":false,"given":"Ruth","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital , Bochum 44791 ,","place":["Germany"]},{"name":"Institute of Neuroradiology, Ruhr-University Bochum, St. Josef-Hospital , Bochum 44791 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya","family":"Ayzenberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital 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