title: Protective and detrimental roles for regulatory T cells in a viral model for multiple sclerosis.
abstract: Multiple sclerosis (MS) has been proposed to be an immune-mediated disease in the central nervous system (CNS) that can be triggered by virus infections. In Theiler's murine encephalomyelitis virus (TMEV) infection, during the first week (acute stage), mice develop polioencephalomyelitis. After 3 weeks (chronic stage), mice develop immune-mediated demyelination with virus persistence, which has been used as a viral model for MS. Regulatory T cells (Tregs) can suppress inflammation, and have been suggested to be protective in immune-mediated diseases, including MS. However, in virus-induced inflammatory demyelination, although Tregs can suppress inflammation, preventing immune-mediated pathology, Tregs may also suppress antiviral immune responses, leading to more active viral replication and/or persistence. To determine the role and potential translational usage of Tregs in MS, we treated TMEV-infected mice with ex vivo generated induced Tregs (iTregs) on day 0 (early) or during the chronic stage (therapeutic). Early treatment worsened clinical signs during acute disease. The exacerbation of acute disease was associated with increased virus titers and decreased immune cell recruitment in the CNS. Therapeutic iTreg treatment reduced inflammatory demyelination during chronic disease. Immunologically, iTreg treatment increased interleukin-10 production from B cells, CD4(+) T cells and dendritic cells, which may contribute to the decreased CNS inflammation.
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Martinez
authors.forename: Fridrik
authors.initials: F
authors.lastname: Karlsson
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Sato
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Kawai
authors.forename: Seiichi
authors.initials: S
authors.lastname: Omura
authors.forename: Alireza
authors.initials: A
authors.lastname: Minagar
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Grisham
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tsunoda
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D018188:Cardiovirus Infections / Q000276:immunology; D004660:Encephalitis / Q000276:immunology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology* / Q000821:virology; D011051:Poliomyelitis / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D017945:Theilovirus / Q000276:immunology
keywords: CNS demyelinating disease; Picornaviridae infections; autoimmunity; immunology; inflammation; regulatory T lymphocyte