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In Autoimmune Diabetes Unique Autoreactive T Cells Recognize Insulin Peptides Generated in the Islets of Langerhans

Besides the genetic framework, there are two critical requirements for the development of tissue-specific autoimmune diseases. First, autoreactive T cells need to escape thymic negative selection. Second, they need to find suitable conditions for autoantigen presentation and activation in the target...

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Detalles Bibliográficos
Autores principales: Mohan, James F., Levisetti, Matteo G., Calderon, Boris, Herzog, Jeremy W., Petzold, Shirley J., Unanue, Emil R.
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080751/
https://www.ncbi.nlm.nih.gov/pubmed/20190756
http://dx.doi.org/10.1038/ni.1850
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author Mohan, James F.
Levisetti, Matteo G.
Calderon, Boris
Herzog, Jeremy W.
Petzold, Shirley J.
Unanue, Emil R.
author_facet Mohan, James F.
Levisetti, Matteo G.
Calderon, Boris
Herzog, Jeremy W.
Petzold, Shirley J.
Unanue, Emil R.
author_sort Mohan, James F.
collection PubMed
description Besides the genetic framework, there are two critical requirements for the development of tissue-specific autoimmune diseases. First, autoreactive T cells need to escape thymic negative selection. Second, they need to find suitable conditions for autoantigen presentation and activation in the target tissue. We show here that these two conditions are fulfilled in diabetic NOD mice. A set of autoreactive CD4(+) T cells specific for an insulin peptide, with the noteworthy feature of not recognizing the insulin protein when processed by the antigen presenting cells (APC) escape thymic control, participate in diabetes and can cause disease. We also find that APCs situated in close contact with the beta cells in the islets of Langerhans bear vesicles with the antigenic insulin peptides and activate the peptide-specific T cells. These findings may be relevant for other cases of endocrine autoimmunity.
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spelling pubmed-30807512011-04-21 In Autoimmune Diabetes Unique Autoreactive T Cells Recognize Insulin Peptides Generated in the Islets of Langerhans Mohan, James F. Levisetti, Matteo G. Calderon, Boris Herzog, Jeremy W. Petzold, Shirley J. Unanue, Emil R. Nat Immunol Article Besides the genetic framework, there are two critical requirements for the development of tissue-specific autoimmune diseases. First, autoreactive T cells need to escape thymic negative selection. Second, they need to find suitable conditions for autoantigen presentation and activation in the target tissue. We show here that these two conditions are fulfilled in diabetic NOD mice. A set of autoreactive CD4(+) T cells specific for an insulin peptide, with the noteworthy feature of not recognizing the insulin protein when processed by the antigen presenting cells (APC) escape thymic control, participate in diabetes and can cause disease. We also find that APCs situated in close contact with the beta cells in the islets of Langerhans bear vesicles with the antigenic insulin peptides and activate the peptide-specific T cells. These findings may be relevant for other cases of endocrine autoimmunity. 2010-02-28 2010-04 /pmc/articles/PMC3080751/ /pubmed/20190756 http://dx.doi.org/10.1038/ni.1850 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Mohan, James F.
Levisetti, Matteo G.
Calderon, Boris
Herzog, Jeremy W.
Petzold, Shirley J.
Unanue, Emil R.
In Autoimmune Diabetes Unique Autoreactive T Cells Recognize Insulin Peptides Generated in the Islets of Langerhans
title In Autoimmune Diabetes Unique Autoreactive T Cells Recognize Insulin Peptides Generated in the Islets of Langerhans
title_full In Autoimmune Diabetes Unique Autoreactive T Cells Recognize Insulin Peptides Generated in the Islets of Langerhans
title_fullStr In Autoimmune Diabetes Unique Autoreactive T Cells Recognize Insulin Peptides Generated in the Islets of Langerhans
title_full_unstemmed In Autoimmune Diabetes Unique Autoreactive T Cells Recognize Insulin Peptides Generated in the Islets of Langerhans
title_short In Autoimmune Diabetes Unique Autoreactive T Cells Recognize Insulin Peptides Generated in the Islets of Langerhans
title_sort in autoimmune diabetes unique autoreactive t cells recognize insulin peptides generated in the islets of langerhans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080751/
https://www.ncbi.nlm.nih.gov/pubmed/20190756
http://dx.doi.org/10.1038/ni.1850
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