Theiler's virus-mediated autoimmunity: local presentation of CNS antigens and epitope spreading

Ann N Y Acad Sci. 2002 Apr;958:26-38.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Autoimmunity / immunology*
  • Cardiovirus Infections / immunology
  • Cardiovirus Infections / pathology
  • Central Nervous System / cytology
  • Central Nervous System / immunology*
  • Epitopes / immunology*
  • Humans
  • Myelin Sheath / immunology
  • T-Lymphocytes / immunology
  • Theilovirus / immunology*

Substances

  • Epitopes