Authors:
Qingyong Ji, Luca Castelli, & Joan M Goverman
Summary:
Myelin presentation to T cells in the central nervous system (CNS) sustains inflammation in multiple sclerosis (MS). CD4+ and CD8+ T cells contribute to MS, but only cells that present myelin to CD4+ T cells have been identified. We show that MHC class I–restricted myelin basic protein (MBP) was presented by oligodendrocytes and cross-presented by Tip–dendritic cells (DCs) during experimental autoimmune encephalomyelitis (EAE), an animal model of MS initiated by CD4+ T cells. Tip-DCs activated naive and effector CD8+ T cells ex vivo, and naive MBP-specific CD8+ T cells were activated in the CNS during CD4+ T cell–induced EAE. These results demonstrate that CD4+ T cell–mediated CNS autoimmunity leads to determinant spreading to myelin-specific CD8+ T cells that can directly recognize oligodendrocytes.
Source:
Nature Immunology; 14, 254-261 (01/06/13)