Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells.

Published

Journal Article

In this study, acute and chronic brain and spinal cord lesions, and normal appearing white matter (NAWM), were resected post-mortem from a patient with aggressive relapsing-remitting multiple sclerosis (MS). T-cell infiltrates from the central nervous system (CNS) lesions and NAWM were separated and characterized in-vitro. All infiltrates showed a proliferative response against multiple myelin peptides. Studies of the T-cell receptor (TCR)Vbeta and Jbeta usage revealed a very skewed repertoire with shared complementarity-determining region (CDR)3 lengths detected in all CNS lesions and NAWM. In the acute lesion, genomic profiling of the infiltrating T-cells revealed up-regulated expression of TCRalpha and beta chain, retinoic acid-related orphan nuclear hormone receptor C (RORC) transcription factor, and multiple cytokine genes that mediate Th17 cell expansion. The differentially expressed genes involved in regulation of Th17 cells represent promising targets for new therapies of relapsing-remitting MS.

Full Text

Duke Authors

Cited Authors

  • Montes, M; Zhang, X; Berthelot, L; Laplaud, D-A; Brouard, S; Jin, J; Rogan, S; Armao, D; Jewells, V; Soulillou, J-P; Markovic-Plese, S

Published Date

  • February 2009

Published In

Volume / Issue

  • 130 / 2

Start / End Page

  • 133 - 144

PubMed ID

  • 18977698

Pubmed Central ID

  • 18977698

Electronic International Standard Serial Number (EISSN)

  • 1521-7035

Digital Object Identifier (DOI)

  • 10.1016/j.clim.2008.08.030

Language

  • eng

Conference Location

  • United States