Published online before print December 21, 2007

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(American Journal of Pathology. 2008;172:146-155.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070690

Interleukin-17 Production in Central Nervous System-Infiltrating T Cells and Glial Cells Is Associated with Active Disease in Multiple Sclerosis

John S. Tzartos^*, Manuel A. Friese, Matthew J. Craner, Jackie Palace, Jia Newcombe^¶, Margaret M. Esiri^* and Lars Fugger^||

From the Departments of Neuropathology^*and Clinical Neurology,John Radcliffe Hospital, and the Medical Research Council Human Immunology Unit,the Neurosciences Group,Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; NeuroResource,^¶University College London, Institute of Neurology, London, United Kingdom; and the Department of Clinical Immunology,||Aarhus University Hospital, Skejby Sygehus, Denmark

Recent findings in the animal model for multiple sclerosis (MS), experimental autoimmune encephalomyelitis, implicate a novel CD4⁺ T-cell subset (T_H17), 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.

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