title: Infection with Mycobacterium bovis BCG diverts traffic of myelin oligodendroglial glycoprotein autoantigen-specific T cells away from the central nervous system and ameliorates experimental autoimmune encephalomyelitis.
abstract: Infectious agents have been proposed to influence susceptibility to autoimmune diseases such as multiple sclerosis. We induced a Th1-mediated central nervous system (CNS) autoimmune disease, experimental autoimmune encephalomyelitis (EAE) in mice with an ongoing infection with Mycobacterium bovis strain bacillus Calmette-Guérin (BCG) to study this possibility. C57BL/6 mice infected with live BCG for 6 weeks were immunized with myelin oligodendroglial glycoprotein peptide (MOG(35-55)) to induce EAE. The clinical severity of EAE was reduced in BCG-infected mice in a BCG dose-dependent manner. Inflammatory-cell infiltration and demyelination of the spinal cord were significantly lessened in BCG-infected animals compared with uninfected EAE controls. ELISPOT and gamma interferon intracellular cytokine analysis of the frequency of antigen-specific CD4(+) T cells in the CNS and in BCG-induced granulomas and adoptive transfer of MOG(35-55)-specific green fluorescent protein-expressing cells into BCG-infected animals indicated that nervous tissue-specific (MOG(35-55)) CD4(+) T cells accumulate in the BCG-induced granuloma sites. These data suggest a novel mechanism for infection-mediated modulation of autoimmunity. We demonstrate that redirected trafficking of activated CNS antigen-specific CD4(+) T cells to local inflammatory sites induced by BCG infection modulates the initiation and progression of a Th1-mediated CNS autoimmune disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, 53706, USA.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Sewell
authors.forename: Emily K
authors.initials: EK
authors.lastname: Reinke
authors.forename: Dominic O
authors.initials: DO
authors.lastname: Co
authors.forename: Laura H
authors.initials: LH
authors.lastname: Hogan
authors.forename: Robert B
authors.initials: RB
authors.lastname: Fritz
authors.forename: Matyas
authors.initials: M
authors.lastname: Sandor
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Fabry
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002465:Cell Movement; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000502:physiology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014375:Tuberculoma / Q000276:immunology; D014376:Tuberculosis / Q000150:complications / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D006023:Glycoproteins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)