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Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes

Every, Alison L., Kramer, David, Mannering, Stuart I., Lew, Andrew M. and Harrison, Leonard C. 2006, Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes, Journal of immunology, vol. 176, no. 8, pp. 4608-4615.

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Title Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes
Author(s) Every, Alison L.
Kramer, David
Mannering, Stuart I.
Lew, Andrew M.
Harrison, Leonard C.
Journal name Journal of immunology
Volume number 176
Issue number 8
Start page 4608
End page 4615
Publisher Williams & Wilkins
Place of publication Baltimore, MD.
Publication date 2006-04
ISSN 0022-1767
1550-6606
Summary Insulin, an autoantigen in type 1 diabetes, when administered mucosally to diabetes-prone NOD mice induces regulatory T cells (Treg) that protect against diabetes. Compared with protein, Ag encoded as DNA has potential advantages as a therapeutic agent. We found that intranasal vaccination of NOD mice with plasmid DNA encoding mouse proinsulin II-induced CD4+ Treg that suppressed diabetes development, both after adoptive cotransfer with "diabetogenic" spleen cells and after transfer into NOD mice given cyclophosphamide to accelerate diabetes onset. In contrast to prototypic CD4+CD25+ Treg, CD4+ Treg induced by proinsulin DNA were both CD25+ and CD25 and not defined by markers such as glucocorticoid-induced TNFR-related protein (GITR), CD103, or Foxp3. Intriguingly, despite induction of Treg and reduced islet inflammation, diabetes incidence in proinsulin DNA-treated mice was unchanged. However, diabetes was prevented when DNA vaccination was performed under the cover of CD40 ligand blockade, known to prevent priming of CTL by mucosal Ag. Thus, intranasal vaccination with proinsulin DNA has therapeutic potential to prevent diabetes, as demonstrated by induction of protective Treg, but further modifications are required to improve its efficacy, which could be compromised by concomitant induction of pathogenic immunity.

Language eng
Field of Research 110703 Autoimmunity
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2006 by The American Association of Immunologists, Inc.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30009067

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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