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Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA vaccination
DNA vaccination is a promising strategy to induce effector T cells but also regulatory Foxp3(+) CD25(+) CD4(+) Treg cells and inhibit autoimmune disorders such as type 1 diabetes. Little is known about the antigen requirements that facilitate priming of Treg cells but not autoreactive effector CD8(+...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942695/ https://www.ncbi.nlm.nih.gov/pubmed/27406624 http://dx.doi.org/10.1038/srep29419 |
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author | Stifter, Katja Schuster, Cornelia Schlosser, Michael Boehm, Bernhard Otto Schirmbeck, Reinhold |
author_facet | Stifter, Katja Schuster, Cornelia Schlosser, Michael Boehm, Bernhard Otto Schirmbeck, Reinhold |
author_sort | Stifter, Katja |
collection | PubMed |
description | DNA vaccination is a promising strategy to induce effector T cells but also regulatory Foxp3(+) CD25(+) CD4(+) Treg cells and inhibit autoimmune disorders such as type 1 diabetes. Little is known about the antigen requirements that facilitate priming of Treg cells but not autoreactive effector CD8(+) T cells. We have shown that the injection of preproinsulin (ppins)-expressing pCI/ppins vector into PD-1- or PD-L1-deficient mice induced K(b)/A12-21-monospecific CD8(+) T cells and autoimmune diabetes. A pCI/ppinsΔA12-21 vector (lacking the critical K(b)/A12-21 epitope) did not induce autoimmune diabetes but elicited a systemic Foxp3(+) CD25(+) Treg cell immunity that suppressed diabetes induction by a subsequent injection of the diabetogenic pCI/ppins. TGF-β expression was significantly enhanced in the Foxp3(+) CD25(+) Treg cell population of vaccinated/ppins-primed mice. Ablation of Treg cells in vaccinated/ppins-primed mice by anti-CD25 antibody treatment abolished the protective effect of the vaccine and enabled diabetes induction by pCI/ppins. Adoptive transfer of Treg cells from vaccinated/ppins-primed mice into PD-L1(−/−) hosts efficiently suppressed diabetes induction by pCI/ppins. We narrowed down the Treg-stimulating domain to a 15-residue ppins76–90 peptide. Vaccine-induced Treg cells thus play a crucial role in the control of de novo primed autoreactive effector CD8(+) T cells in this diabetes model. |
format | Online Article Text |
id | pubmed-4942695 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49426952016-07-20 Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA vaccination Stifter, Katja Schuster, Cornelia Schlosser, Michael Boehm, Bernhard Otto Schirmbeck, Reinhold Sci Rep Article DNA vaccination is a promising strategy to induce effector T cells but also regulatory Foxp3(+) CD25(+) CD4(+) Treg cells and inhibit autoimmune disorders such as type 1 diabetes. Little is known about the antigen requirements that facilitate priming of Treg cells but not autoreactive effector CD8(+) T cells. We have shown that the injection of preproinsulin (ppins)-expressing pCI/ppins vector into PD-1- or PD-L1-deficient mice induced K(b)/A12-21-monospecific CD8(+) T cells and autoimmune diabetes. A pCI/ppinsΔA12-21 vector (lacking the critical K(b)/A12-21 epitope) did not induce autoimmune diabetes but elicited a systemic Foxp3(+) CD25(+) Treg cell immunity that suppressed diabetes induction by a subsequent injection of the diabetogenic pCI/ppins. TGF-β expression was significantly enhanced in the Foxp3(+) CD25(+) Treg cell population of vaccinated/ppins-primed mice. Ablation of Treg cells in vaccinated/ppins-primed mice by anti-CD25 antibody treatment abolished the protective effect of the vaccine and enabled diabetes induction by pCI/ppins. Adoptive transfer of Treg cells from vaccinated/ppins-primed mice into PD-L1(−/−) hosts efficiently suppressed diabetes induction by pCI/ppins. We narrowed down the Treg-stimulating domain to a 15-residue ppins76–90 peptide. Vaccine-induced Treg cells thus play a crucial role in the control of de novo primed autoreactive effector CD8(+) T cells in this diabetes model. Nature Publishing Group 2016-07-11 /pmc/articles/PMC4942695/ /pubmed/27406624 http://dx.doi.org/10.1038/srep29419 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Stifter, Katja Schuster, Cornelia Schlosser, Michael Boehm, Bernhard Otto Schirmbeck, Reinhold Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA vaccination |
title | Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA vaccination |
title_full | Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA vaccination |
title_fullStr | Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA vaccination |
title_full_unstemmed | Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA vaccination |
title_short | Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA vaccination |
title_sort | exploring the induction of preproinsulin-specific foxp3(+) cd4(+) treg cells that inhibit cd8(+) t cell-mediated autoimmune diabetes by dna vaccination |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942695/ https://www.ncbi.nlm.nih.gov/pubmed/27406624 http://dx.doi.org/10.1038/srep29419 |
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