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Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes
Little is known about the events triggering lymphocyte invasion of the pancreatic islets in prelude to autoimmune diabetes. For example, where islet-reactive T cells first encounter antigen has not been identified. We addressed this issue using BDC2.5 T cell receptor transgenic mice, which express a...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1999
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192987/ https://www.ncbi.nlm.nih.gov/pubmed/9892615 |
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author | Höglund, Petter Mintern, Justine Waltzinger, Caroline Heath, William Benoist, Christophe Mathis, Diane |
author_facet | Höglund, Petter Mintern, Justine Waltzinger, Caroline Heath, William Benoist, Christophe Mathis, Diane |
author_sort | Höglund, Petter |
collection | PubMed |
description | Little is known about the events triggering lymphocyte invasion of the pancreatic islets in prelude to autoimmune diabetes. For example, where islet-reactive T cells first encounter antigen has not been identified. We addressed this issue using BDC2.5 T cell receptor transgenic mice, which express a receptor recognizing a natural islet beta cell antigen. In BDC2.5 animals, activated T cells were found only in the islets and the lymph nodes draining them, and there was a close temporal correlation between lymph node T cell activation and islet infiltration. When naive BDC2.5 T cells were transferred into nontransgenic recipients, proliferating cells were observed only in pancreatic lymph nodes, and this occurred significantly before insulitis was detectable. Surprisingly, proliferation was not seen in 10-day-old recipients. This age-dependent dichotomy was reproduced in a second transfer system based on an unrelated antigen artificially expressed on beta cells. We conclude that beta cell antigens are transported specifically to pancreatic lymph nodes, where they trigger reactive T cells to invade the islets. Systemic or extrapancreatic T cell priming, indicative of activation via molecular mimicry or superantigens, was not seen. Compromised presentation of beta cell antigens in the pancreatic lymph nodes of juvenile animals may be the root of a first “checkpoint” in diabetes progression. |
format | Text |
id | pubmed-2192987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21929872008-04-16 Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes Höglund, Petter Mintern, Justine Waltzinger, Caroline Heath, William Benoist, Christophe Mathis, Diane J Exp Med Articles Little is known about the events triggering lymphocyte invasion of the pancreatic islets in prelude to autoimmune diabetes. For example, where islet-reactive T cells first encounter antigen has not been identified. We addressed this issue using BDC2.5 T cell receptor transgenic mice, which express a receptor recognizing a natural islet beta cell antigen. In BDC2.5 animals, activated T cells were found only in the islets and the lymph nodes draining them, and there was a close temporal correlation between lymph node T cell activation and islet infiltration. When naive BDC2.5 T cells were transferred into nontransgenic recipients, proliferating cells were observed only in pancreatic lymph nodes, and this occurred significantly before insulitis was detectable. Surprisingly, proliferation was not seen in 10-day-old recipients. This age-dependent dichotomy was reproduced in a second transfer system based on an unrelated antigen artificially expressed on beta cells. We conclude that beta cell antigens are transported specifically to pancreatic lymph nodes, where they trigger reactive T cells to invade the islets. Systemic or extrapancreatic T cell priming, indicative of activation via molecular mimicry or superantigens, was not seen. Compromised presentation of beta cell antigens in the pancreatic lymph nodes of juvenile animals may be the root of a first “checkpoint” in diabetes progression. The Rockefeller University Press 1999-01-18 /pmc/articles/PMC2192987/ /pubmed/9892615 Text en 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/). |
spellingShingle | Articles Höglund, Petter Mintern, Justine Waltzinger, Caroline Heath, William Benoist, Christophe Mathis, Diane Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes |
title | Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes |
title_full | Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes |
title_fullStr | Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes |
title_full_unstemmed | Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes |
title_short | Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes |
title_sort | initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192987/ https://www.ncbi.nlm.nih.gov/pubmed/9892615 |
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