Article abstract
Nature Immunology 8, 172 - 180 (2007)
Published online: 7 January 2007 | doi:10.1038/ni1430
CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize CD4+ TH-17 cells in relapsing EAE
Samantha L Bailey1, Bettina Schreiner1, Eileen J McMahon2 & Stephen D Miller1
Abstract
Peripherally derived CD11b+ myeloid dendritic cells (mDCs), plasmacytoid DCs, CD8
+ DCs and macrophages accumulate in the central nervous system during relapsing experimental autoimmune encephalomyelitis (EAE). During acute relapsing EAE induced by a proteolipid protein peptide of amino acids 178–191, transgenic T cells (139TCR cells) specific for the relapse epitope consisting of proteolipid protein peptide amino acids 139–151 clustered with mDCs in the central nervous system, were activated and differentiated into T helper cells producing interleukin 17 (TH-17 cells). CNS mDCs presented endogenously acquired peptide, driving the proliferation of and production of interleukin 17 by naive 139TCR cells in vitro and in vivo. The mDCs uniquely biased TH-17 and not TH1 differentiation, correlating with their enhanced expression of transforming growth factor-
1 and interleukins 6 and 23. Plasmacytoid DCs and CD8+ DCs were superior to macrophages but were much less efficient than mDCs in presenting endogenous peptide to induce TH-17 cells. Our findings indicate a critical function for CNS mDCs in driving relapses in relapsing EAE.
- Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
- Present address: Biology Department, Westmont College, Santa Barbara, California 93108, USA.
Correspondence to: Stephen D Miller1 e-mail: s-d-miller@northwestern.edu
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