Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis - PubMed (original) (raw)
doi: 10.1038/nm1202. Epub 2005 Feb 27.
Affiliations
- PMID: 15735651
- DOI: 10.1038/nm1202
Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis
Eileen J McMahon et al. Nat Med. 2005 Mar.
Abstract
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.
Comment in
- Multiple sclerosis: trapped in deadly glue.
Platten M, Steinman L. Platten M, et al. Nat Med. 2005 Mar;11(3):252-3. doi: 10.1038/nm0305-252. Nat Med. 2005. PMID: 15746934 No abstract available.
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