title: CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells.
abstract: T cell tolerance to parenchymal self-antigens is thought to be induced by encounter of the T cell with its cognate peptide-major histocompatibility complex (MHC) ligand expressed on the parenchymal cell, which lacks appropriate costimulatory function. We have used a model system in which naive T cell receptor (TCR) transgenic hemagglutinin (HA)-specific CD4+ T cells are adoptively transferred into mice expressing HA as a self-antigen on parenchymal cells. After transfer, HA-specific T cells develop a phenotype indicative of TCR engagement and are rendered functionally tolerant. However, T cell tolerance is not induced by peptide-MHC complexes expressed on parenchymal cells. Rather, tolerance induction requires that HA is presented by bone marrow (BM)-derived cells. These results indicate that tolerance induction to parenchymal self-antigens requires transfer to a BM-derived antigen-presenting cell that presents it to T cells in a tolerogenic fashion.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Adler
authors.forename: D W
authors.initials: DW
authors.lastname: Marsh
authors.forename: G S
authors.initials: GS
authors.lastname: Yochum
authors.forename: J L
authors.initials: JL
authors.lastname: Guzzo
authors.forename: A
authors.initials: A
authors.lastname: Nigam
authors.forename: W G
authors.initials: WG
authors.lastname: Nelson
authors.forename: D M
authors.initials: DM
authors.lastname: Pardoll
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D001324:Autoantigens