CD4 super(+) T Cell Tolerance to Parenchymal Self-Antigens Requires Presentation by Bone Marrow-derived Antigen-presenting Cells

• Published in: The Journal of experimental medicine Vol. 187; no. 10; pp. 1555 - 1564
• Main Authors: Adler, A J, Marsh, D W, Yochum, G S, Guzzo, J L, Nigam, A, Nelson, W G, Pardoll, D M
• Format: Journal Article
• Language: English
• Published: 01.05.1998
• ISSN: 0022-1007

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 super(+) 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.