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-Independent Manner1
* Department of Pathology and Laboratory Medicine and
Cellular and Molecular Pathology Program, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53706
Multiple sclerosis and an animal model resembling multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases of the CNS that are suppressed by systemic mycobacterial infection in mice and BCG vaccination in humans. Host defense responses against Mycobacterium in mice are influenced by T lymphocytes and their cytokine products, particularly IFN-
, which plays a protective regulatory role in EAE. To analyze the counter-regulatory role of mycobacterial infection-induced IFN- in the CNS on the function of the pathological Th17 cells and the clinical outcome of EAE, we induced EAE in mice that were intracerebrally infected with Mycobacterium bovis bacille Calmette-Guerin (BCG). In this study, we demonstrate that intracerebral (i.c.) BCG infection prevented inflammatory cell recruitment to the spinal cord and suppressed the development of EAE. Concomitantly, there was a significant decrease in the frequency of myelin oligodendrocyte glycoprotein-specific IFN--producing CD4+ T cells in the CNS. IL-17+CD4+ T cell responses were significantly suppressed in i.c. BCG-infected mice following EAE induction regardless of T cell specificity. The frequency of Foxp3+CD4+ T cells in these mice was equivalent to that of control mice. Intracerebral BCG infection-induced protection of EAE and suppression of myelin oligodendrocyte glycoprotein-specific IL-17+CD4+ T cell responses were similar in both wild-type and IFN--deficient mice. These data show that live BCG infection in the brain suppresses CNS autoimmunity. These findings also reveal that the regulation of Th17-mediated autoimmunity in the CNS can be independent of IFN--mediated mechanisms.
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 by U. S. Public Health Service National Institutes of Health Research Grant NS-37570 and NMSS Grant PP 1429 (to Z.F.).
2 Current address: Department of Orthopaedics, Vanderbilt University, 1215 21st Avenue S., Nashville, TN 37232.
3 Current address: Department of Neurology, Bayerische Julius-Maximilians-Universitaet Wuerzburg, Josef-Schneider Strasse 11 97080, Wuerzburg, Germany.
4 Address correspondence and reprint requests to Dr. Zsuzsanna Fabry, University of Wisconsin-Madison School of Medicine and Public Health, Department of Pathology and Laboratory Medicine, 1300 University Avenue, 6130 Medical Science Center, Madison, WI 53706. E-mail address: zfabry{at}wisc.edu
5 Abbreviations used in this paper: BCG, Mycobacterium bovis bacille Calmette-Guerin; EAE, experimental autoimmune encephalomyelitis; MS, multiple sclerosis; MOG, myelin oligodendrocyte glycoprotein; i.c., intracerebral; LFB, luxol fast blue; CLN, cervical lymph node; WT, wild type; Mtb, Mycobacterium tuberculosis.
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  S. Guo, D. Cobb, and R. B. Smeltz T-bet Inhibits the In Vivo Differentiation of Parasite-Specific CD4+ Th17 Cells in a T Cell-Intrinsic Manner J. Immunol., May 15, 2009; 182(10): 6179 - 6186. [Abstract] [Full Text] [PDF]
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