Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1782300716181749760 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3900547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT eberwineryana autoantigeninducedfocusingofvb13tcellsprecedesonsetofautoimmunediabetesinthelew1wr1rat AT cortlaura autoantigeninducedfocusingofvb13tcellsprecedesonsetofautoimmunediabetesinthelew1wr1rat AT habibmichael autoantigeninducedfocusingofvb13tcellsprecedesonsetofautoimmunediabetesinthelew1wr1rat AT mordesjohnp autoantigeninducedfocusingofvb13tcellsprecedesonsetofautoimmunediabetesinthelew1wr1rat AT blankenhornelizabethp autoantigeninducedfocusingofvb13tcellsprecedesonsetofautoimmunediabetesinthelew1wr1rat |