title: Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis.
abstract: Recent findings in the animal model for multiple sclerosis (MS), experimental autoimmune encephalomyelitis, implicate a novel CD4+ T-cell subset (TH17), characterized by the secretion of interleukin-17 (IL-17), in disease pathogenesis. To elucidate its role in MS, brain tissues from patients with MS were compared to controls. We detected expression of IL-17 mRNA (by in situ hybridization) and protein (by immunohistochemistry) in perivascular lymphocytes as well as in astrocytes and oligodendrocytes located in the active areas of MS lesions. Further, we found a significant increase in the number of IL-17+ T cells in active rather than inactive areas of MS lesions. Specifically, double immunofluorescence showed that IL-17 immunoreactivity was detected in 79% of T cells in acute lesions, 73% in active areas of chronic active lesions, but in only 17% of those in inactive lesions and 7% in lymph node control tissue. CD8+, as well as CD4+, T cells were equally immunostained for IL-17 in MS tissues. Interestingly, and in contrast to lymph node T cells, no perivascular T cells showed FoxP3 expression, a marker of regulatory T cells, at any stage of MS lesions. These observations suggest an enrichment of both IL-17+CD4+ and CD8+ T cells in active MS lesions as well as an important role for IL-17 in MS pathogenesis, with some remarkable differences from the experimental autoimmune encephalomyelitis model.
authors.affiliation: Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: John S
authors.initials: JS
authors.lastname: Tzartos
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Friese
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Craner
authors.forename: Jackie
authors.initials: J
authors.lastname: Palace
authors.forename: Jia
authors.initials: J
authors.lastname: Newcombe
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Esiri
authors.forename: Lars
authors.initials: L
authors.lastname: Fugger
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002490:Central Nervous System / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D009457:Neuroglia / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17