CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells

Adam J. Adler, David W. Marsh, Gregory S. Yochum, James L. Guzzo, Ankesh Nigam, William G. Nelson, Drew M. Pardoll

Research output: Contribution to journalArticlepeer-review

240 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1555-1564
Number of pages10
JournalJournal of Experimental Medicine
Volume187
Issue number10
DOIs
StatePublished - May 18 1998

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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