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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*{dagger}, Manuel A. Friese{dagger}{ddagger}, Matthew J. Craner{sect}, Jackie Palace{dagger}, Jia Newcombe, Margaret M. Esiri*@, and Lars Fugger{dagger}{ddagger}||

From the Departments of Neuropathology* and Clinical Neurology,{dagger} John Radcliffe Hospital, and the Medical Research Council Human Immunology Unit,{ddagger} the Neurosciences Group,{sect} 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 (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.




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