Antigen presentation in the CNS by myeloid dendritic cells drives progression of relapsing experimental autoimmune encephalomyelitis

Stephen D. Miller*, Eileen J. McMahon, Bettina Schreiner, Samantha L. Bailey

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

111 Scopus citations

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 endogenousmyelin 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 REAE shows that peripherally derived CD11b+CD11c +CD45hi 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-CD45hi macrophages, but less efficient than mDCs at presenting endogenous peptide to induce Th17 cells. In contrast, CNS-resident CD11b+CD11c-CD45low microglia purified from the inflamed CNS were found to be largely incapable of activating either naïve or effector T cells.

Original languageEnglish (US)
Title of host publicationHow Do We Best Employ Animal Models for Type 1 Diabetesand Multiple Sclerosis
PublisherBlackwell Publishing Inc.
Pages179-191
Number of pages13
ISBN (Print)1573316784, 9781573316781
DOIs
StatePublished - Apr 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1103
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Antigen presentation
  • Central nervous system
  • Dendritic cells
  • Epitope spreading
  • Experimental autoimmune encephalomyelitis
  • Multiple sclerosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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