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

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2009-02, Vol.130 (2), p.133-144
• Main Authors: Montes, Monica, Zhang, Xin, Berthelot, Laureline, Laplaud, David-Axel, Brouard, Sophie, Jin, Jianping, Rogan, Sarah, Armao, Diane, Jewells, Valerie, Soulillou, Jean-Paul, Markovic-Plese, Silva
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Autoimmunity; Biological and medical sciences; Central Nervous System - immunology; Central Nervous System - pathology; Child; Demyelinating CNS inflammatory lesions; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Profiling; Human; Humans; Interleukin-17 - genetics; Interleukin-17 - immunology; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Relapsing-Remitting - genetics; Multiple Sclerosis, Relapsing-Remitting - immunology; Multiple Sclerosis, Relapsing-Remitting - pathology; Myelin Sheath - immunology; Myelin Sheath - metabolism; Neurology; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Receptors, Cytokine - genetics; Receptors, Cytokine - immunology; T-cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Transcription Factors - genetics; Transcription Factors - immunology
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2008.08.030

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)Vβ and Jβ 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 TCRα and β 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.