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

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.