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(+...
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| Format: | Journal Article |
| Language: | English |
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2016
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| Online Access: | https://hdl.handle.net/10356/83796 http://hdl.handle.net/10220/41458 |
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| author | Stifter, Katja Schuster, Cornelia Schlosser, Michael Boehm, Bernhard Otto Schirmbeck, Reinhold |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Stifter, Katja Schuster, Cornelia Schlosser, Michael Boehm, Bernhard Otto Schirmbeck, Reinhold |
| author_sort | Stifter, Katja |
| collection | NTU |
| 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. |
| first_indexed | 2025-02-19T03:44:46Z |
| format | Journal Article |
| id | ntu-10356/83796 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:44:46Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/837962022-02-16T16:26:33Z 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 Lee Kong Chian School of Medicine (LKCMedicine) Immunization Protein design 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. Published version 2016-09-21T04:36:51Z 2019-12-06T15:32:14Z 2016-09-21T04:36:51Z 2019-12-06T15:32:14Z 2016 Journal Article 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-. 2045-2322 https://hdl.handle.net/10356/83796 http://hdl.handle.net/10220/41458 10.1038/srep29419 27406624 en Scientific Reports © 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/ 12 p. application/pdf |
| spellingShingle | Immunization Protein design 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 | Immunization Protein design |
| url | https://hdl.handle.net/10356/83796 http://hdl.handle.net/10220/41458 |
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