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- W2210346 abstract "Abstract Intramuscular (i.m.) vaccination with plasmid DNA (pDNA) encoding beta cell autoantigens such as glutamic acid decarboxylase 65 (GAD65) is an approach to suppress ongoing Type 1 diabetes (T1D) in NOD mice. However, protection is dependent on co-treatment with pDNAs encoding IL-4 and/or IL-10, and the subsequent induction of type 2 CD4+ T effectors. To enhance the therapeutic efficacy of pDNA vaccination, we explored epidermal delivery of pDNA via “gene gun”. Notably, reports have shown induction of a preferential type 2-like CD4+ T cell response when pDNA encoding antigen-only is delivered to the epidermis via gene gun. We hypothesized that biolistic delivery of pDNA would preferentially induce type 2 CD4+ T effectors and suppress established beta cell autoimmunity in NOD mice. Groups of 10 wk-old NOD female mice were treated four times with pDNA encoding GAD65-Ig (pGAD65) administered i.m. or delivered by gene gun on 1.6 uM gold particles. Whereas i.m. injection of pGAD65 resulted in preferential induction of GAD65-specific CD4+ Th1 cells and no protection against T1D, the majority of NOD mice treated with gene gun delivered pGAD65 remained diabetes-free and protection correlated with increased GAD65-specific IL-4 secreting CD4+ T cells. These results demonstrate that gene-gun delivered pDNA encoding beta cell autoantigen-only is an effective strategy to induce immunoregulatory CD4+ T cells and suppress T1D." @default.
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- W2210346 date "2007-04-01" @default.
- W2210346 modified "2023-10-18" @default.
- W2210346 title "Expansion of GAD65–Specific Immunoregulatory Effector Cells by Biolistic-Mediated Gene Delivery Prevents Autoimmune Diabetes in NOD Mice (131.14)" @default.
- W2210346 doi "https://doi.org/10.4049/jimmunol.178.supp.131.14" @default.
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