Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity

The mechanisms that determine whether receptor stimulation leads to lymphocyte tolerance versus activation remain poorly understood. We have used rat insulin promoter (RIP)-gp/P14 double-transgenic mice expressing the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) on pancreatic β-islet...

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Main Authors:	Garza, Kristine M., Chan, Steven M., Suri, Rakesh, Nguyen, Linh T., Odermatt, Bernhard, Schoenberger, Stephen P., Ohashi, Pamela S.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2000
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213533/

id	pubmed-2213533
recordtype	oai_dc
spelling	pubmed-22135332008-04-16 Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity Garza, Kristine M. Chan, Steven M. Suri, Rakesh Nguyen, Linh T. Odermatt, Bernhard Schoenberger, Stephen P. Ohashi, Pamela S. Brief Definitive Report The mechanisms that determine whether receptor stimulation leads to lymphocyte tolerance versus activation remain poorly understood. We have used rat insulin promoter (RIP)-gp/P14 double-transgenic mice expressing the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) on pancreatic β-islet cells together with T cells expressing an LCMV-gp–specific T cell receptor to assess the requirements for the induction of autoimmunity. Our studies have shown that administration of the gp peptide gp33 leads to the activation of P14-transgenic T cells, as measured by the upregulation of activation markers and the induction of effector cytotoxic activity. This treatment also leads to expansion and deletion of P14 T cells. Despite the induction of cytotoxic T lymphocyte activity, peptide administration is not sufficient to induce diabetes. However, the administration of gp peptide together with an activating anti-CD40 antibody rapidly induces diabetes. These findings suggest that the induction of tolerance versus autoimmunity is determined by resting versus activated antigen-presenting cells. The Rockefeller University Press 2000-06-05 /pmc/articles/PMC2213533/ /pubmed/10839816 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Garza, Kristine M. Chan, Steven M. Suri, Rakesh Nguyen, Linh T. Odermatt, Bernhard Schoenberger, Stephen P. Ohashi, Pamela S.
spellingShingle	Garza, Kristine M. Chan, Steven M. Suri, Rakesh Nguyen, Linh T. Odermatt, Bernhard Schoenberger, Stephen P. Ohashi, Pamela S. Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity
author_facet	Garza, Kristine M. Chan, Steven M. Suri, Rakesh Nguyen, Linh T. Odermatt, Bernhard Schoenberger, Stephen P. Ohashi, Pamela S.
author_sort	Garza, Kristine M.
title	Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity
title_short	Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity
title_full	Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity
title_fullStr	Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity
title_full_unstemmed	Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity
title_sort	role of antigen-presenting cells in mediating tolerance and autoimmunity
description	The mechanisms that determine whether receptor stimulation leads to lymphocyte tolerance versus activation remain poorly understood. We have used rat insulin promoter (RIP)-gp/P14 double-transgenic mice expressing the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) on pancreatic β-islet cells together with T cells expressing an LCMV-gp–specific T cell receptor to assess the requirements for the induction of autoimmunity. Our studies have shown that administration of the gp peptide gp33 leads to the activation of P14-transgenic T cells, as measured by the upregulation of activation markers and the induction of effector cytotoxic activity. This treatment also leads to expansion and deletion of P14 T cells. Despite the induction of cytotoxic T lymphocyte activity, peptide administration is not sufficient to induce diabetes. However, the administration of gp peptide together with an activating anti-CD40 antibody rapidly induces diabetes. These findings suggest that the induction of tolerance versus autoimmunity is determined by resting versus activated antigen-presenting cells.
publisher	The Rockefeller University Press
publishDate	2000
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213533/
_version_	1611434753350696960

Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity

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