Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/83796
Title: Exploring the induction of preproinsulin-specific Foxp3+ CD4+ Treg cells that inhibit CD8+ T cell-mediated autoimmune diabetes by DNA vaccination
Authors: Stifter, Katja
Schuster, Cornelia
Schlosser, Michael
Boehm, Bernhard Otto
Schirmbeck, Reinhold
Keywords: Immunization
Protein design
Issue Date: 2016
Source: Stifter, K., Schuster, C., Schlosser, M., Boehm, B. O., & Schirmbeck, R. (2016). Exploring the induction of preproinsulin-specific Foxp3+ CD4+ Treg cells that inhibit CD8+ T cell-mediated autoimmune diabetes by DNA vaccination. Scientific Reports, 6, 29419-.
Series/Report no.: Scientific Reports
Abstract: 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.
URI: https://hdl.handle.net/10356/83796
http://hdl.handle.net/10220/41458
ISSN: 2045-2322
DOI: 10.1038/srep29419
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2016 The Authors. 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/
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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