Crosspresentation by nonhematopoietic and direct presentation by hematopoietic cells induce central tolerance to myelin basic protein.
Central tolerance plays a critical role in eliminating self-reactive T cells specific for peripheral antigens. Here we show that central tolerance of MHC class I-restricted T cells specific for classic myelin basic protein (MBP), a component of the myelin sheath, is mediated by both bone marrow (BM)-derived and nonBM-derived cells. Unexpectedly, BM-derived cells induce tolerance directly by using classic MBP that they synthesize, whereas nonBM-derived cells mediate tolerance by crosspresenting classic MBP acquired from an exogenous source. Thus, tolerance to tissue-specific antigens can involve multiple cell types and mechanisms in the thymus, which may account for the limited spectrum of autoimmune syndromes observed when expression of tissue-specific antigens is impaired only in thymic epithelial cells.
Perchellet
Antoine
A
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Brabb
Thea
T
Goverman
Joan M
JM
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D017353:Gene Deletion; D006056:Golgi Apparatus / Q000276:immunology; D006413:Hematopoietic System / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D004676:Myelin Basic Protein
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