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Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes

In this paper, we test the hypothesis that triggering of a second T cell receptor (TCR) expressed on diabetogenic T cells might initiate the onset of diabetes. A cross between two TCR-transgenic strains, the BDC2.5 strain that carries diabetogenic TCRs and the A18 strain that carries receptors speci...

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Autores principales: Fossati, Gianluca, Cooke, Anne, Papafio, Ruby Quartey, Haskins, Kathryn, Stockinger, Brigitta
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195608/
https://www.ncbi.nlm.nih.gov/pubmed/10449528
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author Fossati, Gianluca
Cooke, Anne
Papafio, Ruby Quartey
Haskins, Kathryn
Stockinger, Brigitta
author_facet Fossati, Gianluca
Cooke, Anne
Papafio, Ruby Quartey
Haskins, Kathryn
Stockinger, Brigitta
author_sort Fossati, Gianluca
collection PubMed
description In this paper, we test the hypothesis that triggering of a second T cell receptor (TCR) expressed on diabetogenic T cells might initiate the onset of diabetes. A cross between two TCR-transgenic strains, the BDC2.5 strain that carries diabetogenic TCRs and the A18 strain that carries receptors specific for C5, was set up to monitor development of diabetes after activation through the C5 TCR. F1 BDC2.5 × A18 mice developed diabetes spontaneously beyond 3–4 mo of age. Although their T cells express both TCRs constitutively, the A18 receptor is expressed at extremely low levels. In vitro activation of dual TCR T cells followed by adoptive transfer into neonatal or adult F1 mice resulted in diabetes onset and death within 10 d after transfer. In contrast, in vivo immunization of F1 mice with different forms of C5 antigen not only failed to induce diabetes but protected mice from the spontaneous onset of diabetes. We propose that antigenic stimulation of cells with low levels of TCR produces signals inadequate for full activation, resulting instead in anergy.
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spelling pubmed-21956082008-04-16 Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes Fossati, Gianluca Cooke, Anne Papafio, Ruby Quartey Haskins, Kathryn Stockinger, Brigitta J Exp Med Original Article In this paper, we test the hypothesis that triggering of a second T cell receptor (TCR) expressed on diabetogenic T cells might initiate the onset of diabetes. A cross between two TCR-transgenic strains, the BDC2.5 strain that carries diabetogenic TCRs and the A18 strain that carries receptors specific for C5, was set up to monitor development of diabetes after activation through the C5 TCR. F1 BDC2.5 × A18 mice developed diabetes spontaneously beyond 3–4 mo of age. Although their T cells express both TCRs constitutively, the A18 receptor is expressed at extremely low levels. In vitro activation of dual TCR T cells followed by adoptive transfer into neonatal or adult F1 mice resulted in diabetes onset and death within 10 d after transfer. In contrast, in vivo immunization of F1 mice with different forms of C5 antigen not only failed to induce diabetes but protected mice from the spontaneous onset of diabetes. We propose that antigenic stimulation of cells with low levels of TCR produces signals inadequate for full activation, resulting instead in anergy. The Rockefeller University Press 1999-08-16 /pmc/articles/PMC2195608/ /pubmed/10449528 Text en © 1999 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/).
spellingShingle Original Article
Fossati, Gianluca
Cooke, Anne
Papafio, Ruby Quartey
Haskins, Kathryn
Stockinger, Brigitta
Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes
title Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes
title_full Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes
title_fullStr Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes
title_full_unstemmed Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes
title_short Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes
title_sort triggering a second t cell receptor on diabetogenic t cells can prevent induction of diabetes
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195608/
https://www.ncbi.nlm.nih.gov/pubmed/10449528
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