Planas R, Metz I, Ortiz Y, Vilarrasa N, Jelcíc I, Salinas-Riester G, Heesen C, Brück W, Martin R, Sospedra M.

OBJECTIVE: Multiple sclerosis (MS) is a disease of the central nervous system with marked heterogeneity in several aspects including pathological processes.Based on infiltrating immune cells, deposition of humoral factors and loss of oligodendrocytes and/or myelin proteins, four lesion patterns have been described. Pattern II is characterized by antibody and complement deposition in addition to T-cell infiltration. MS is considered a T-cell-mediated disease,but until now the study of pathogenic T cells has encountered major challenges,most importantly the limited access of brain-infiltrating T cells. Our objective was to identify, isolate, and characterize brain-infiltrating clonally expanded T-cells in pattern II MS lesions. METHODS: We used next-generation sequencing to identify clonally expanded T cells in demyelinating pattern II brain autopsy lesions, subsequently isolated these as T-cell clones from autologous cerebrospinal fluid and functionally characterized them. RESULTS: We identified clonally expanded CD8 +but also CD4+ T cells in demyelinating pattern II lesions and for the first time were able to isolate these as live T-cell clones. The functional characterization shows that T cells releasing Th2 cytokines and able to provide B cell help dominate the T-cell infiltrate in pattern II brain lesions. INTERPRETATION: Our data provide the first functional evidence for a putative role of Th2/Tc2 cells in pattern II MS supporting the existence of this pathogenic pheno-type and questioning the protective role that is generally ascribed to Th2 cells.Our observations are important to consider for future treatments of pattern

Ann. Neurol. 2015;2(9):875-93

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