Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes
HLA class II-restricted regulatory T cell (Treg) epitopes in IgG (also called “Tregitopes”) have been reported to suppress immune responses to coadministered antigens by stimulating the expansion of natural Tregs (nTregs). Here we evaluate their impact on human immune responses to islet cell antigen...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2013/621693 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832547453477322752 |
|---|---|
| author | Leslie P. Cousens Yan Su Elizabeth McClaine Xin Li Frances Terry Robert Smith Jinhee Lee William Martin David W. Scott Anne S. De Groot |
| author_facet | Leslie P. Cousens Yan Su Elizabeth McClaine Xin Li Frances Terry Robert Smith Jinhee Lee William Martin David W. Scott Anne S. De Groot |
| author_sort | Leslie P. Cousens |
| collection | DOAJ |
| description | HLA class II-restricted regulatory T cell (Treg) epitopes in IgG (also called “Tregitopes”) have been reported to suppress immune responses to coadministered antigens by stimulating the expansion of natural Tregs (nTregs). Here we evaluate their impact on human immune responses to islet cell antigens ex vivo and on the modulation of type 1 diabetes (T1D) in a murine model in vivo. Co-administration of Tregitopes and T1D antigens delayed development of hyperglycemia and reduced the incidence of diabetes in NOD mice. Suppression of diabetes could be observed even following onset of disease. To measure the impact of Tregitope treatment on T cell responses, we evaluated the effect of Tregitope treatment in DO11.10 mice. Upregulation of FoxP3 in KJ1-26-stained OVA-specific CD4+ T cells was observed following treatment of DO11.10 mice with Tregitopes, along with reductions in anti-OVA Ig and T effector responses. In ex vivo studies of human T cells, peripheral blood mononuclear cells’ (PBMC) responses to GAD65 epitopes in the presence and absence of Tregitope were variable. Suppression of immune responses to GAD65 epitopes ex vivo by Tregitope appeared to be more effective in assays using PBMC from a newly diagnosed diabetic subject than for other more established diabetic subjects, and correlation of the degree of suppression with predicted HLA restriction of the Tregitopes was confirmed. Implementation of these defined regulatory T cell epitopes for therapy of T1D and other autoimmune diseases may lead to a paradigm shift in disease management. |
| format | Article |
| id | doaj-art-99873e973b884496902fded50d1c2bd4 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-99873e973b884496902fded50d1c2bd42025-02-03T06:44:48ZengWileyJournal of Diabetes Research2314-67452314-67532013-01-01201310.1155/2013/621693621693Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 DiabetesLeslie P. Cousens0Yan Su1Elizabeth McClaine2Xin Li3Frances Terry4Robert Smith5Jinhee Lee6William Martin7David W. Scott8Anne S. De Groot9EpiVax, Inc., 146 Clifford Street, Providence, RI 02903, USAUniversity of Maryland School of Medicine, Baltimore, MD 21201, USAEpiVax, Inc., 146 Clifford Street, Providence, RI 02903, USAUniversity of Maryland School of Medicine, Baltimore, MD 21201, USAEpiVax, Inc., 146 Clifford Street, Providence, RI 02903, USAAlpert Medical School of Brown University, Providence, RI 02912, USAUniversity of Massachusetts Medical School, Worcester, MA 01655, USAEpiVax, Inc., 146 Clifford Street, Providence, RI 02903, USAUniversity of Maryland School of Medicine, Baltimore, MD 21201, USAEpiVax, Inc., 146 Clifford Street, Providence, RI 02903, USAHLA class II-restricted regulatory T cell (Treg) epitopes in IgG (also called “Tregitopes”) have been reported to suppress immune responses to coadministered antigens by stimulating the expansion of natural Tregs (nTregs). Here we evaluate their impact on human immune responses to islet cell antigens ex vivo and on the modulation of type 1 diabetes (T1D) in a murine model in vivo. Co-administration of Tregitopes and T1D antigens delayed development of hyperglycemia and reduced the incidence of diabetes in NOD mice. Suppression of diabetes could be observed even following onset of disease. To measure the impact of Tregitope treatment on T cell responses, we evaluated the effect of Tregitope treatment in DO11.10 mice. Upregulation of FoxP3 in KJ1-26-stained OVA-specific CD4+ T cells was observed following treatment of DO11.10 mice with Tregitopes, along with reductions in anti-OVA Ig and T effector responses. In ex vivo studies of human T cells, peripheral blood mononuclear cells’ (PBMC) responses to GAD65 epitopes in the presence and absence of Tregitope were variable. Suppression of immune responses to GAD65 epitopes ex vivo by Tregitope appeared to be more effective in assays using PBMC from a newly diagnosed diabetic subject than for other more established diabetic subjects, and correlation of the degree of suppression with predicted HLA restriction of the Tregitopes was confirmed. Implementation of these defined regulatory T cell epitopes for therapy of T1D and other autoimmune diseases may lead to a paradigm shift in disease management.http://dx.doi.org/10.1155/2013/621693 |
| spellingShingle | Leslie P. Cousens Yan Su Elizabeth McClaine Xin Li Frances Terry Robert Smith Jinhee Lee William Martin David W. Scott Anne S. De Groot Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes Journal of Diabetes Research |
| title | Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes |
| title_full | Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes |
| title_fullStr | Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes |
| title_full_unstemmed | Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes |
| title_short | Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes |
| title_sort | application of igg derived natural treg epitopes igg tregitopes to antigen specific tolerance induction in a murine model of type 1 diabetes |
| url | http://dx.doi.org/10.1155/2013/621693 |
| work_keys_str_mv | AT lesliepcousens applicationofiggderivednaturaltregepitopesiggtregitopestoantigenspecifictoleranceinductioninamurinemodeloftype1diabetes AT yansu applicationofiggderivednaturaltregepitopesiggtregitopestoantigenspecifictoleranceinductioninamurinemodeloftype1diabetes AT elizabethmcclaine applicationofiggderivednaturaltregepitopesiggtregitopestoantigenspecifictoleranceinductioninamurinemodeloftype1diabetes AT xinli applicationofiggderivednaturaltregepitopesiggtregitopestoantigenspecifictoleranceinductioninamurinemodeloftype1diabetes AT francesterry applicationofiggderivednaturaltregepitopesiggtregitopestoantigenspecifictoleranceinductioninamurinemodeloftype1diabetes AT robertsmith applicationofiggderivednaturaltregepitopesiggtregitopestoantigenspecifictoleranceinductioninamurinemodeloftype1diabetes AT jinheelee applicationofiggderivednaturaltregepitopesiggtregitopestoantigenspecifictoleranceinductioninamurinemodeloftype1diabetes AT williammartin applicationofiggderivednaturaltregepitopesiggtregitopestoantigenspecifictoleranceinductioninamurinemodeloftype1diabetes AT davidwscott applicationofiggderivednaturaltregepitopesiggtregitopestoantigenspecifictoleranceinductioninamurinemodeloftype1diabetes AT annesdegroot applicationofiggderivednaturaltregepitopesiggtregitopestoantigenspecifictoleranceinductioninamurinemodeloftype1diabetes |