CD4+ T Cell Tolerance to Parenchymal Self-Antigens Requires Presentation by Bone Marrow–derived Antigen-presenting Cells
Year: 1998
Type: article
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: Adam J. Adler, David W. Marsh, Gregory S. Yochum, James L. Guzzo, Ankesh Nigam, William G. Nelson, Drew M. Pardoll
Institutions: Johns Hopkins University, Johns Hopkins Medicine
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funder: National Cancer Institute
Awards: G4183297229, G582469399
OpenAlex ID: W2090168014