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Autoantigen-Induced Focusing of Vβ13(+) T Cells Precedes Onset of Autoimmune Diabetes in the LEW.1WR1 Rat

The earliest events leading to autoimmune type 1 diabetes (T1D) are not known in any species. A T-cell receptor (TCR)-variable region, TCR-Vβ13, is required for susceptibility to autoimmune diabetes in rats, and selective depletion of Vβ13(+) T cells with an allele-specific monoclonal antibody preve...

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Autores principales: Eberwine, Ryan A., Cort, Laura, Habib, Michael, Mordes, John P., Blankenhorn, Elizabeth P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900547/
https://www.ncbi.nlm.nih.gov/pubmed/24150607
http://dx.doi.org/10.2337/db13-0462
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author Eberwine, Ryan A.
Cort, Laura
Habib, Michael
Mordes, John P.
Blankenhorn, Elizabeth P.
author_facet Eberwine, Ryan A.
Cort, Laura
Habib, Michael
Mordes, John P.
Blankenhorn, Elizabeth P.
author_sort Eberwine, Ryan A.
collection PubMed
description The earliest events leading to autoimmune type 1 diabetes (T1D) are not known in any species. A T-cell receptor (TCR)-variable region, TCR-Vβ13, is required for susceptibility to autoimmune diabetes in rats, and selective depletion of Vβ13(+) T cells with an allele-specific monoclonal antibody prevents disease in multiple rat strains. To investigate the role of Vβ13 early in diabetes, we examined islet T-cell transcripts in susceptible (LEW.1WR1) and resistant (LEW.1W and Wistar Furth) strains induced with polyinosinic:polycytidylic acid. Vβ13(+) T cells displayed antigenic focusing in LEW.1WR1 islets 5 days postinduction and were characterized by a substantial decrease in complementarity determining region 3 diversity. This occurred prior to significant islet T-cell accumulation (day 7) or frank diabetes (days 10–14). Vβ13(+) transcripts increased in LEW.1WR1 islets during diabetes progression, but not in resistant rats. We also analyzed transcript clonality of rat TCR-Vα5, an ortholog of the dominant TCR-Vα chain found on insulin B:9-23–reactive T cells in nonobese diabetic rat islets. We observed clonal expansion of Vα5(+) transcripts in prediabetic LEW.1WR1 islets, suggesting that rat Vα5 is also an important component of islet autoantigen recognition. These data provide additional evidence that genome-encoded TCR sequences are important determinants of genetic susceptibility to T1D.
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spelling pubmed-39005472015-02-01 Autoantigen-Induced Focusing of Vβ13(+) T Cells Precedes Onset of Autoimmune Diabetes in the LEW.1WR1 Rat Eberwine, Ryan A. Cort, Laura Habib, Michael Mordes, John P. Blankenhorn, Elizabeth P. Diabetes Islet Studies The earliest events leading to autoimmune type 1 diabetes (T1D) are not known in any species. A T-cell receptor (TCR)-variable region, TCR-Vβ13, is required for susceptibility to autoimmune diabetes in rats, and selective depletion of Vβ13(+) T cells with an allele-specific monoclonal antibody prevents disease in multiple rat strains. To investigate the role of Vβ13 early in diabetes, we examined islet T-cell transcripts in susceptible (LEW.1WR1) and resistant (LEW.1W and Wistar Furth) strains induced with polyinosinic:polycytidylic acid. Vβ13(+) T cells displayed antigenic focusing in LEW.1WR1 islets 5 days postinduction and were characterized by a substantial decrease in complementarity determining region 3 diversity. This occurred prior to significant islet T-cell accumulation (day 7) or frank diabetes (days 10–14). Vβ13(+) transcripts increased in LEW.1WR1 islets during diabetes progression, but not in resistant rats. We also analyzed transcript clonality of rat TCR-Vα5, an ortholog of the dominant TCR-Vα chain found on insulin B:9-23–reactive T cells in nonobese diabetic rat islets. We observed clonal expansion of Vα5(+) transcripts in prediabetic LEW.1WR1 islets, suggesting that rat Vα5 is also an important component of islet autoantigen recognition. These data provide additional evidence that genome-encoded TCR sequences are important determinants of genetic susceptibility to T1D. American Diabetes Association 2014-02 2014-01-16 /pmc/articles/PMC3900547/ /pubmed/24150607 http://dx.doi.org/10.2337/db13-0462 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Islet Studies
Eberwine, Ryan A.
Cort, Laura
Habib, Michael
Mordes, John P.
Blankenhorn, Elizabeth P.
Autoantigen-Induced Focusing of Vβ13(+) T Cells Precedes Onset of Autoimmune Diabetes in the LEW.1WR1 Rat
title Autoantigen-Induced Focusing of Vβ13(+) T Cells Precedes Onset of Autoimmune Diabetes in the LEW.1WR1 Rat
title_full Autoantigen-Induced Focusing of Vβ13(+) T Cells Precedes Onset of Autoimmune Diabetes in the LEW.1WR1 Rat
title_fullStr Autoantigen-Induced Focusing of Vβ13(+) T Cells Precedes Onset of Autoimmune Diabetes in the LEW.1WR1 Rat
title_full_unstemmed Autoantigen-Induced Focusing of Vβ13(+) T Cells Precedes Onset of Autoimmune Diabetes in the LEW.1WR1 Rat
title_short Autoantigen-Induced Focusing of Vβ13(+) T Cells Precedes Onset of Autoimmune Diabetes in the LEW.1WR1 Rat
title_sort autoantigen-induced focusing of vβ13(+) t cells precedes onset of autoimmune diabetes in the lew.1wr1 rat
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900547/
https://www.ncbi.nlm.nih.gov/pubmed/24150607
http://dx.doi.org/10.2337/db13-0462
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