Immunol Cell Biol 2002 Feb;80(1):14-20
Weir CR, Nicolson K, Backstrom BT.
Malaghan Institute of Medical Research,Wellington School of Medicine, Wellington, New Zealand.
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.