Published online before print December 21, 2007

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Copyright © 2008 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2008.070690

Accepted for publication October 16, 2007.

Article

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

^@ To whom correspondence should be addressed. E-mail: margaret.esiri{at}clneuro.ox.ac.uk.

	Abstract

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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