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Antigen Presentation in the CNS by Myeloid Dendritic Cells Drives Progression of Relapsing Experimental Autoimmune Encephalomyelitis
Author(s) -
MILLER STEPHEN D.,
McMAHON EILEEN J.,
SCHREINER BETTINA,
BAILEY SAMANTHA L.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1394.023
Subject(s) - epitope , experimental autoimmune encephalomyelitis , cd11c , immunology , myelin oligodendrocyte glycoprotein , myelin , antigen presentation , antigen , antigen presenting cell , biology , t cell , microglia , cross presentation , myelin basic protein , microbiology and biotechnology , immune system , central nervous system , inflammation , neuroscience , biochemistry , gene , phenotype
Abstract : Chronic progression of relapsing experimental autoimmune encephalomyelitis (R‐EAE), a mouse model of multiple sclerosis (MS), is dependent on the activation of T cells to endogenous myelin epitopes, that is, epitope spreading. This review focuses on the cellular and molecular mechanisms underlying the process of epitope spreading. Surprisingly, activation of naïve T cells to endogenous myelin epitopes in SJL mice undergoing R‐EAE occurs directly in the central nervous system (CNS), a site generally perceived to be immunologically privileged. Determination of the antigen presentation capacity of antigen‐presenting cell (APC) populations purified from the CNS of mice with established R‐EAE shows that peripherally derived CD11b + CD11c + CD45 hi myeloid dendritic cells (mDCs) most efficiently present endogenous myelin antigens to activate both preactivated effector myelin‐specific T cells and naïve T cells. The mDCs, which drive epitope spreading, preferentially polarize pathogenic Th17 responses correlating with their enhanced expression of TGF‐β1, IL‐6, and IL‐23. Both B220 + CD11c + plasmacytoid (pDCs) and CD8α + CD11c + (CD8 DCs) were superior to CD11b + CD11c – CD45 hi macrophages, but less efficient than mDCs at presenting endogenous peptide to induce Th17 cells. In contrast, CNS‐resident CD11b + CD11c – CD45 low microglia purified from the inflamed CNS were found to be largely incapable of activating either naïve or effector T cells.