Th17 immunity has been shown to regulate autoimmune diabetes in mice. IL-17 neutralization prevented development of diabetes when given postinitiation of insulitis but not earlier, suggesting interference with the effector phase of the disease. Islet-cell Ag-specific Th17 cells converted into IFN-γ–secreting Th1-like cells and caused diabetes in mice recipients. The role of IL-17 in human type 1 diabetes (T1D) is, however, not established. In this study, we show upregulation of Th17 immunity in peripheral blood T cells from children with T1D. This was characterized by increased IL-17 secretion and expression of IL-17, IL-22, and retinoic acid-related orphan receptor C isoform 2, but also FOXP3 transcripts upon T cell activation in vitro. Also, circulating memory CD4 cells from children with T1D showed the same pattern of IL-17, IL-22 and FOXP3 mRNA upregulation, indicating IL-17 pathway activation in vivo. IL-17–positive T cells appeared to be CD4+ cells expressing TCR-αβ and CCR6, and a subpopulation showed coproduction of IFN-γ. Given the Th17 immunity in T1D, we demonstrated that IL-17 had detrimental effects on human islet cells in vitro; it potentiated both inflammatory and proapoptotic responses. Our findings highlight the role of IL-17 immunity in the pathogenesis of human T1D and point to a potential therapeutic strategy.

No abstract

No abstract

Ultraviolet ͑UV͒ irradiation of HI-doped xenon matrix dissociates the precursor and leads to the formation and trapping of neutral atoms. After UV photolysis, annealing of the matrix mobilizes the hydrogen atoms at about 38 K. The mobilized hydrogen atoms react with I/Xe centers forming HXeI molecules in a diffusion controlled reaction. The formed molecules can be photolyzed with infrared ͑IR͒ irradiation at 2950-3800 cm Ϫ1 and quantitatively regenerated thermally. The formation of HXeI from neutral atoms is proved by the quantitative correlation between neutral iodine atoms and HXeI molecules in selective IR photodissociation and thermal regeneration experiments. Kinetic measurements show that the formation of HXeI from atoms is prevented by a potential barrier, which is estimated to be 700 cm Ϫ1 in magnitude. The potential barrier is proposed to originate from the avoided crossing between neutral HϩXeϩI and ionic ͑HXe͒ ϩ ϩI Ϫ singlet surfaces. The dissociation energy D 0 of HXeI with respect to the top of the potential barrier is estimated to be 2950 cm Ϫ1 and D e about 4070 cm Ϫ1 in solid Xe. The weak IR photodissociation profile of HXeI around 3000 cm Ϫ1 is measured by irradiating the sample with tunable IR source and monitoring the changes in the fundamental region. The formation mechanism from neutral atoms is believed to be valid for other similar rare-gas compounds.