Defects in Antigen-Presenting Cells in the BB-DP Rat Model of Diabetes

Type-1 diabetes is the result of a T cell mediated immune response against the insulin-producing β cells in the islet of Langerhans. In humans, until now, the disease is only clearly detectable at the onset of the disease. Therefore studies to identify initial factors involved in the etio-pathogenesis are impossible in humans prone to develop diabetes. In order to study the early, prodromal phases of type-1 diabetes we used a spontaneous rodent animal model of the disease, the Biobreeding-Diabetes Prone (BB-DP) rat. This rat develops diabetes, because it is in particular defective for a population of regulatory T cells, the ART2+ regulatory T cells and because it possesses the disease-prone MHC haplotype RT1u (iddm1). We investigated (Chapter 2) the myeloid dendritic cells (DC) in this animal model, since DC, the antigen-presenting cells par excellence, are able to elicit immune responses from naïve T cells and are known to be involved in autoimmune responses because they are capable of modulating immunity versus tolerance. We studied bone-marrow precursor derived myeloid DC of three BB-DP rat sub-lines (Worcester, Groningen, Seattle) to identify defects in these DC, which could be responsible for the defective tolerance induction towards diabetes-associated islet autoantigens in this rat model. We found that the myeloid DC generated from bone-marrow precursors were defective in these three BB- DP rat sub-lines, showing an immature, more macrophage-like phenotype, a low MHC class II expression on their surface, a reduced T cell stimulatory capacity, a reduced capability to differentiate into fully mature DC and a reduced production of the immunosuppressive cytokine IL-10 as compared to two control rat strains (Wistar, F344). We assume that such DC defects contribute to the decreased tolerance towards islet autoantigens in the autoimmune diabetes of the BB-DP rat, since such defective DC are in particular defective to stimulate ART2+ regulatory T cells sufficiently. We

Variable BCG efficacy in rhesus populations: Pulmonary BCG provides protection where standard intra-dermal vaccination fails

Pathogenesis and treatment of chronic pulmonary disease

Acute stress syndrome of the yellow European eel (Anguilla anguilla Linnaes) when exposed to a graded swimming-load

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Efficient Induction of Antitumor Immunity by Synthetic Toll-like Receptor Ligand-Peptide Conjugates

Tumorimmunolog