Pro-apoptotic DNA vaccination ameliorates new onset of autoimmune diabetes in NOD mice and induces foxp3+ regulatory T cells in vitro

Vaccine
Alice F LiAlan Escher

Abstract

We have shown previously that incorporation of a cDNA coding for the pro-apoptotic protein BAX into plasmid DNA coding for a secreted form of the pancreatic beta-cell antigen glutamic acid decarboxylase (GAD) promotes prevention of type 1 diabetes in non-obese diabetic (NOD) mice. Here we present evidence indicating that injection of the same vaccine at time of early diabetes onset could ameliorate the disease with efficacy, with 42% of mice overtly diabetic by 40 weeks of age compared to 92% in control groups. In addition, immunological analysis revealed that the DNA vaccine induced CD4(+)CD25(+) T cells cultured from draining lymph nodes that had immunosuppressive function in vitro. The induced regulatory T cells (Tregs) expressed the foxp3 gene and showed cell-contact-dependent as well as TGF-beta- and IL-10-independent immunosuppressive activity. Data also revealed that CD4(+)CD25(-) T cells from mice immunized with the DNA vaccine yielded a cell population that was foxp3(+), showed increased expression of CD25 compared to control, and had immunosuppressive function in vitro, indicating that Tregs could have developed from antigen-induced, peripheral T lymphocytes. In contrast, injection of DNA coding for SGAD55 or BAX alon...Continue Reading

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Citations

Feb 5, 2014·Immunotherapy·Xiaoxiao Wan, Habib Zaghouani
Feb 23, 2012·Cold Spring Harbor Perspectives in Medicine·Xavier Clemente-CasaresPere Santamaria
May 1, 2008·Expert Review of Vaccines·Rajesh Kumar, Edith A Burns
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Apr 9, 2010·Expert Opinion on Biological Therapy·Alice F Li, Alan Escher
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