Experimental autoimmune encephalomyelitis induction in naive mice by dendritic cells presenting a self-peptide.
Self-reactive T cells escape deletion in the thymus and are found in the peripheral repertoire. Because bone-marrow-derived dendritic cells (BM-DC) are potent activators of antigen-specific T cells, these cells could theoretically activate self-reactive T cells leading to autoimmunity. We investigated whether BM-DC could induce the autoimmune disease experimental autoimmune encephalomyelitis (EAE). Our results show that transfer of BM-DC presenting a self-peptide from the myelin oligodendrocyte glycoprotein (MOG35-55) into naive mice induced EAE 7-14 days later. MOG35-55-specific T cells of the Th1 phenotype were present in the lymph nodes and spleens of mice that received live peptide-pulsed BM-DC. Heat-killed or formaldehyde-fixed BM-DC presenting MOG35-55 could induce neither clinical signs of EAE nor a measurable T-cell response in vitro. These data show that live BM-DC presenting a self-antigen can induce the organ-specific autoimmune disorder EAE in a non-transgenic system. Therefore, this new EAE model could be used as a more clinically relevant model for the human disease multiple sclerosis. These findings could also have implications for the use of DC immunotherapy in a clinical setting.
Weir
Catherine R
CR
Malaghan Institute of Medical Research, Wellington School of Medicine, Wellington, New Zealand.
Nicolson
Kirsty
K
Bäckström
B Thomas
BT
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D001324:Autoantigens; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides; C445081:myelin oligodendrocyte glycoprotein (35-55)