CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize CD4+ T(H)-17 cells in relapsing EAE.
Peripherally derived CD11b(+) myeloid dendritic cells (mDCs), plasmacytoid DCs, CD8alpha(+) 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 (T(H)-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 T(H)-17 and not T(H)1 differentiation, correlating with their enhanced expression of transforming growth factor-beta1 and interleukins 6 and 23. Plasmacytoid DCs and CD8alpha(+) DCs were superior to macrophages but were much less efficient than mDCs in presenting endogenous peptide to induce T(H)-17 cells. Our findings indicate a critical function for CNS mDCs in driving relapses in relapsing EAE.
Bailey
Samantha L
SL
Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Schreiner
Bettina
B
McMahon
Eileen J
EJ
Miller
Stephen D
SD
D000818:Animals; D002454:Cell Differentiation; D002490:Central Nervous System / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D005260:Female; D051379:Mice; D009185:Myelin Proteins / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D012008:Recurrence; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D016207:Cytokines; D009185:Myelin Proteins; D010446:Peptide Fragments