Age-dependent T cell tolerance and autoimmunity to myelin basic protein.
Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is induced by activating a subset of myelin basic protein (MBP)-specific T cells that have escaped tolerance induction. Here, we define the tolerance mechanisms that eliminate the majority of MBP-specific T cells from the periphery. We show that MBP-specific T cells undergo central tolerance mediated by bone marrow-derived antigen-presenting cells presenting exogenously derived MBP epitopes. The efficiency of tolerance is age dependent, reflecting the developmentally regulated expression of MBP. Dependence of tolerance on the amount of MBP expressed in vivo results in an age window of susceptibility to EAE in mice that peaks during puberty. These results suggest that factors regulating expression of self-antigens in vivo can influence susceptibility to autoimmunity.
Huseby
E S
ES
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Sather
B
B
Huseby
P G
PG
Goverman
J
J
D000375:Aging / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018628:Gene Dosage; D007108:Immune Tolerance / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012741:Sexual Maturation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C425925:myelin basic protein 121-150