Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis

Nat Med. 2005 Mar;11(3):335-9. doi: 10.1038/nm1202. Epub 2005 Feb 27.


Chronic progression of two T cell-mediated central nervous system (CNS) demyelinating models of multiple sclerosis, relapsing EAE (R-EAE) and Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is dependent on the activation of T cells to endogenous myelin epitopes (epitope spreading). Using transfer of carboxyfluorescein succinyl ester (CFSE)-labeled T-cell receptor (TCR)-transgenic T cells and mixed bone marrow chimeras, we show that activation of naive proteolipid protein (PLP)139-151-specific T cells in SJL mice undergoing PLP178-191-induced R-EAE or TMEV-IDD occurs directly in the CNS and not in the cervical lymph nodes or other peripheral lymphoid organs. Examination of the antigen-presentation capacity of antigen-presenting cell (APC) populations purified from the CNS of mice with PLP178-191-induced R-EAE shows that only F4/80-CD11c+CD45hi dendritic cells (DCs) efficiently present endogenous antigen to activate naive PLP139-151-specific T cells in vitro. In contrast, DCs as well as F4/80+CD45hi macrophages and F4/80+CD45lo microglia activate a PLP139-151-specific helper T cell line. The data suggest that naive T cells enter the inflamed CNS and are activated by local APCs, possibly DCs, to initiate epitope spreading.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation*
  • Cardiovirus Infections / immunology
  • Central Nervous System / immunology*
  • Central Nervous System / pathology
  • Demyelinating Diseases / immunology*
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Epitopes / immunology*
  • Female
  • Mice
  • Multiple Sclerosis / immunology*
  • T-Lymphocytes / immunology
  • Theilovirus


  • Epitopes