| First Author | McMahon EJ | Year | 2005 |
| Journal | Nat Med | Volume | 11 |
| Issue | 3 | Pages | 335-9 |
| PubMed ID | 15735651 | Mgi Jnum | J:97117 |
| Mgi Id | MGI:3574273 | Doi | 10.1038/nm1202 |
| Citation | McMahon EJ, et al. (2005) Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat Med 11(3):335-339 |
| abstractText | 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. |
