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* University of Edinburgh, Institute of Immunology and Infection Research, School of Biological Sciences, Edinburgh, United Kingdom;
Department of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, Bristol, United Kingdom; and
University of Edinburgh, Centre for Inflammation Research and Centre for Multiple Sclerosis Research, Queen’s Medical Research Institute, Edinburgh, U.K.
It has recently been proposed that experimental autoimmune encephalomyelitis, once considered the classical Th1 disease, is predominantly Th17 driven. In this study we show that myelin-reactive Th1 preparations devoid of contaminating IL-17+ cells are highly pathogenic. In contrast, Th17 preparations lacking IFN-
+ cells do not cause disease. Our key observation is that only Th1 cells can access the noninflamed CNS. Once Th1 cells establish the experimental autoimmune encephalomyelitis lesion, Th17 cells appear in the CNS. These data shed important new light on the ability of Th1 vs Th17 cells to access inflamed vs normal tissue. Because the IL-17-triggered release of chemokines by stromal cells could attract many other immune cells, allowing Th17 cells to access the tissues only under conditions of inflammation may be a key process limiting (auto)immune pathology. This has major implications for the design of therapeutic interventions, many of which are now aiming at Th17 rather than Th1 cells.
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1 This work was supported by grants form the Medical Research Council (U.K.) and the Wellcome Trust. C.A.S. is supported by the Batchworth Trust. S.M.A. is a Medical Research Council Senior Research Fellow and a Research Councils U.K. Fellow in Translational Medicine.
2 C.T.P., C.A.S., and C.W.Z.L. contributed equally to this study.
3 Address correspondence and reprint requests to Dr. Stephen M. Anderton, University of Edinburgh, Ashworth Laboratories, Kings Buildings, West Mains Road, Edinburgh EH9 3JT, U.K. E-mail address: steve.anderton{at}ed.ac.uk
4 Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; Ac, acetylated; MBP, myelin basic protein; pMOG, myelin oligodendrocyte glycoprotein peptide.
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