Eomesodermin-expressing CD4 Th cells and association with multiple sclerosis progression and brain atrophy

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Abstract Multiple sclerosis is a chronic inflammatory disease affecting the central nervous system. 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.

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