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

doi:doi:10.1038/nm1202

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 PLP_178–191-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 PLP_178–191-induced R-EAE shows that only F4/80^-CD11c⁺CD45^hi dendritic cells (DCs) efficiently present endogenous antigen to activate naive PLP_139–151-specific T cells in vitro. In contrast, DCs as well as F4/80⁺CD45^hi macrophages and F4/80⁺CD45^lo microglia activate a PLP_139–151-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.

Access

Letter

Article Links

Article Tools

Search Pubmed for