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Originally published online as doi:10.2353/ajpath.2008.070690 on December 21, 2007

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*{dagger}, Manuel A. Friese{dagger}{ddagger}, Matthew J. Craner§, 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,§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 (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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