Open AccessCentral role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions
Author(s) -
Planas Raquel,
Metz Imke,
Ortiz Yaneth,
Vilarrasa Nuria,
Jelčić Ilijas,
SalinasRiester Gabriela,
Heesen Christoph,
Brück Wolfgang,
Martin Roland,
Sospedra Mireia
Publication year - 2015
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.218
Subject(s) - multiple sclerosis , myelin , t cell , cd8 , immune system , antibody , demyelinating disease , medicine , immunology , pathology , phenotype , central nervous system , biology , neuroscience , gene , biochemistry
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 CD 8 + but also CD 4 + 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.