Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells.
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.
Montes
Monica
M
Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Zhang
Xin
X
Berthelot
Laureline
L
Laplaud
David-Axel
DA
Brouard
Sophie
S
Jin
Jianping
J
Rogan
Sarah
S
Armao
Diane
D
Jewells
Valerie
V
Soulillou
Jean-Paul
JP
Markovic-Plese
Silva
S
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
D020381:Interleukin-17; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018121:Receptors, Cytokine; D014157:Transcription Factors