Theiler's virus-mediated autoimmunity: local presentation of CNS antigens and epitope spreading.
Theiler's murine encephalomyelitis virus (TMEV), a natural mouse pathogen, is a neurotropic picornavirus that induces a chronic, CD4+ T cell-mediated demyelinating disease with a clinical course and histopathology similar to those of chronic-progressive multiple sclerosis. Upon infection, TMEV-specific CD4+ T cells target persistent viral antigens in the CNS and initiate myelin damage. Later in the disease, myelin-specific CD4+ T cells are primed by epitope spreading, and these autoimmune T cells contribute to the pathogenesis of the chronic-progressive disease. This review focuses upon aspects of the initiation of a virally induced CD4+ T cell-mediated autoimmune response. First, the steps involved in the hierarchical activation of non-cross-reactive myelin-specific T cells in the SJL/J mouse after CNS infection with TMEV and the role of these autoreactive T cells in chronic myelin damage are discussed. Second, the process of epitope spreading and the role of CNS antigen presenting cells in the temporal presentation of self-antigens is considered. Finally, we will discuss aspects of T cell activation and antigen presentation, and how they can impact autoimmune disease.
Tompkins
S Mark
SM
Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Fuller
Kevin G
KG
Miller
Stephen D
SD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D018188:Cardiovirus Infections / Q000276:immunology / Q000473:pathology; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D009186:Myelin Sheath / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D017945:Theilovirus / Q000276:immunology*
D000939:Epitopes