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

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

Research output: Contribution to journalArticle

238 Citations (Scopus)

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

Fingerprint

Autoantigens
Antigen Presentation
Antigen-Presenting Cells
Bone Marrow
Hemagglutinins
T-Lymphocytes
T-Cell Antigen Receptor
Major Histocompatibility Complex
Peptides
Bone Marrow Cells
Ligands
Phenotype

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Adler, Adam J. ; Marsh, David W. ; Yochum, Gregory ; Guzzo, James L. ; Nigam, Ankesh ; Nelson, William G. ; Pardoll, Drew M. / CD4 + T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells In: Journal of Experimental Medicine. 1998 ; Vol. 187, No. 10. pp. 1555-1564.
@article{03c9fc973d1f4bbb9b2af72cecaa2b76,
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.",
author = "Adler, {Adam J.} and Marsh, {David W.} and Gregory Yochum and Guzzo, {James L.} and Ankesh Nigam and Nelson, {William G.} and Pardoll, {Drew M.}",
year = "1998",
month = "5",
day = "18",
doi = "10.1084/jem.187.10.1555",
language = "English (US)",
volume = "187",
pages = "1555--1564",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "10",

}

CD4 + T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells . / Adler, Adam J.; Marsh, David W.; Yochum, Gregory; Guzzo, James L.; Nigam, Ankesh; Nelson, William G.; Pardoll, Drew M.

In: Journal of Experimental Medicine, Vol. 187, No. 10, 18.05.1998, p. 1555-1564.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CD4 + T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells

AU - Adler, Adam J.

AU - Marsh, David W.

AU - Yochum, Gregory

AU - Guzzo, James L.

AU - Nigam, Ankesh

AU - Nelson, William G.

AU - Pardoll, Drew M.

PY - 1998/5/18

Y1 - 1998/5/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0032543225&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032543225&partnerID=8YFLogxK

U2 - 10.1084/jem.187.10.1555

DO - 10.1084/jem.187.10.1555

M3 - Article

VL - 187

SP - 1555

EP - 1564

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 10

ER -