title: Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neuroimmunology and MS Research (nims), Department of Neurology, University Zurich Frauenklinikstrasse 26, 8091, Zürich, Switzerland.
authors.forename: Raquel
authors.initials: R
authors.lastname: Planas
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen Göttingen, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Metz
authors.affiliation: Neuroimmunology and MS Research (nims), Department of Neurology, University Zurich Frauenklinikstrasse 26, 8091, Zürich, Switzerland.
authors.forename: Yaneth
authors.initials: Y
authors.lastname: Ortiz
authors.affiliation: Neuroimmunology and MS Research (nims), Department of Neurology, University Zurich Frauenklinikstrasse 26, 8091, Zürich, Switzerland.
authors.forename: Nuria
authors.initials: N
authors.lastname: Vilarrasa
authors.affiliation: Neuroimmunology and MS Research (nims), Department of Neurology, University Zurich Frauenklinikstrasse 26, 8091, Zürich, Switzerland.
authors.forename: Ilijas
authors.initials: I
authors.lastname: Jelčić
authors.affiliation: Department of Developmental Biochemistry, DNA Microarray and Deep-Sequencing Facility, Faculty of Medicine, University Medical Center Göttingen Göttingen, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Salinas-Riester
authors.affiliation: Institute for Neuroimmunology and Clinical MS Research (inims), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf Falkenried 94, 20251, Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Heesen
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen Göttingen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.affiliation: Neuroimmunology and MS Research (nims), Department of Neurology, University Zurich Frauenklinikstrasse 26, 8091, Zürich, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.affiliation: Neuroimmunology and MS Research (nims), Department of Neurology, University Zurich Frauenklinikstrasse 26, 8091, Zürich, Switzerland.
authors.forename: Mireia
authors.initials: M
authors.lastname: Sospedra