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Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Planas R Metz I Ortiz Y Vilarrasa N Jelčić I Salinas-Riester G Heesen C Brück W Martin R So,
Project Unraveling the immune etiology of multiple sclerosis - UnmetMS
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Original article (peer-reviewed)

Journal Ann Clin Transl Neurol.
Page(s) 875
Title of proceedings Ann Clin Transl Neurol.

Open Access

URL http://www.ncbi.nlm.nih.gov/pubmed/26401510
Type of Open Access Publisher (Gold Open Access)

Abstract

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 phenotype and questioning the protective role that is generally ascribed to Th2 cells. Our observations are important to consider for future treatments of pattern II MS patients.
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