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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...
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/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. |
format | Text |
id | pubmed-2195608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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