CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells.
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.
Adler
A J
AJ
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Marsh
D W
DW
Yochum
G S
GS
Guzzo
J L
JL
Nigam
A
A
Nelson
W G
WG
Pardoll
D M
DM
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
D001324:Autoantigens