Induction of long-term tolerance to β-cell autoantigens has been investigated both in animal models and in human type 1 diabetes (T1D) in order to prevent the disease. As regards external compounds, the dietary plant protein fraction has been associated with high penetrance of the disease, whereas gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4(+)Foxp3(+) T cells and even more significant induction of γδ T cells in mucosal, but not in non-mucosal lymphoid compartments. This prevention strategy was characterized by an increased proportion of IL-10 and a decreased proportion of IL-2, IL-4 and IFN-γ-positive CD4(+)Foxp3(+) T cells, and IFN-γ-positive γδ T cells, preferentially in mucosal lymphoid organs. In conclusion, i.n. vaccination with gliadin, an environmental antigen with possible etiological influence in T1D, may represent a novel, safer strategy for prevention or even early cure of T1D.

Section of Biomedicine Department of Veterinary Disease Biology Faculty of Health and Medical Sciences University of Copenhagen Frederiksberg Denmark

The Bartholin Instituttet Rigshospitalet Copenhagen Denmark

The Bartholin Instituttet Rigshospitalet Copenhagen Denmark; Department of Immunology and Gnotobiology Institute of Microbiology v v i Academy of Sciences of the Czech Republic Prague Czech Republic

The Bartholin Instituttet Rigshospitalet Copenhagen Denmark; Department of Immunology and Gnotobiology Institute of Microbiology v v i Academy of Sciences of the Czech Republic Prague Czech Republic; ENT Department of the 3rd Faculty of Medicine Charles University and the Central Military Hospital Prague Czech Republic

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