title: Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells.
abstract: 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.
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Montes
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Laureline
authors.initials: L
authors.lastname: Berthelot
authors.forename: David-Axel
authors.initials: DA
authors.lastname: Laplaud
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
authors.forename: Jianping
authors.initials: J
authors.lastname: Jin
authors.forename: Sarah
authors.initials: S
authors.lastname: Rogan
authors.forename: Diane
authors.initials: D
authors.lastname: Armao
authors.forename: Valerie
authors.initials: V
authors.lastname: Jewells
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
authors.forename: Silva
authors.initials: S
authors.lastname: Markovic-Plese
mesh_terms: D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: D020381:Interleukin-17; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018121:Receptors, Cytokine; D014157:Transcription Factors