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* Department of Molecular Biology and Pharmacology, Washington University, St. Louis, MO 63110; and
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, has long been thought to be mediated by Th1 CD4+ T cells. Using adoptive transfer techniques, transfer of CNS specific Th1 T cells was sufficient to induce EAE in naive mice. However, recent studies found a vital role for IL-17 in induction of EAE. These studies suggested that a fraction of IL-17-producing T cells that contaminate Th1 polarized cell lines are largely responsible for initiation of EAE. In this study, we tracked the appearance and cytokine production capacity of adoptively transferred cells within the CNS of mice throughout EAE disease. IL-17-producing, adoptively transferred cells were not enriched over the low percentages present in vitro. Thus, there was no selective recruitment and/or preferential proliferation of adoptively transferred IL-17-producing cells during the induction of EAE. Instead a large number of CNS infiltrating host T cells in mice with EAE were capable of producing IL-17 following ex vivo stimulation. The IL-17-producing T cells contained both 
β and 
TCR+ T cells with a CD4+CD8– or CD4–CD8– phenotype. These cells concentrated within the CNS within 3 days of adoptive transfer, and appeared to play a role in EAE induction as adoptive transfer of Th1 lines derived from wild-type mice into IL-17-deficient mice induced reduced EAE clinical outcomes. This study demonstrates that an encephalitogenic Th1 cell line induces recruitment of host IL-17-producing T cells to the CNS during the initiation of EAE and that these cells contribute to the incidence and severity of disease.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by a National Multiple Sclerosis Society Fellowship, Grants RG 3314, RG 3732, and CA 1012 from the National Multiple Sclerosis Society, and a W. M. Keck Fellowship in Molecular Medicine at St. Louis.
2 Address correspondence and reprint requests to Dr. John H. Russell, Washington University, 660 South Euclid Avenue, St. Louis, MO 63110. E-mail address: jrussell{at}wustl.edu
3 Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; MS, multiple sclerosis; KO, knockout; WT, wild type; MOG, myelin oligodendrocyte glycoprotein.
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