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Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes
Joint Authors
McClaine, Elizabeth
Scott, David W.
Su, Yan
Lee, Jinhee
Terry, Frances
Cousens, Leslie P.
Martin, William
Smith, Robert
De Groot, Anne S.
Li, Xin
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-04-23
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Cousens, Leslie P.& Su, Yan& McClaine, Elizabeth& Li, Xin& Terry, Frances& Smith, Robert…[et al.]. 2013. 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،Vol. 2013, no. 2013, pp.1-17.
https://search.emarefa.net/detail/BIM-1005936
Modern Language Association (MLA)
Cousens, Leslie P.…[et al.]. 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 No. 2013 (2013), pp.1-17.
https://search.emarefa.net/detail/BIM-1005936
American Medical Association (AMA)
Cousens, Leslie P.& Su, Yan& McClaine, Elizabeth& Li, Xin& Terry, Frances& Smith, Robert…[et al.]. 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. 2013. Vol. 2013, no. 2013, pp.1-17.
https://search.emarefa.net/detail/BIM-1005936
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1005936