Ann N Y Acad Sci 2002 Apr;958:26-38
Tompkins SM, Fuller KG, Miller SD.
Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
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.