We therefore hypothesized that the protective effect in our model could be due to transfer and survival of partially mismatched lymphocytes from pups to the mother during delivery. Despite the potential for such a mechanism in our model, we found no evidence of persistent chimeric CD4+ or CD8+ lymphocytes from paternal origin within the dams’ spleens to support this. As we examined spleens at the end of follow-up it is possible that such cells were transferred, but were not persistent. It is also possible that other cell types such as antigen-presenting cells

or cells in other organs are relevant in the process. An alternative hypothesis is that processing of paternal placental antigens within the maternal circulation leads to increases in the maternal regulatory T cell population [22,23] and that effects on diabetes development are mediated Fluorouracil solubility dmso by such regulatory T cells. In summary, this study C59 wnt manufacturer demonstrates that gestation has no enhancing effects on pre-existent autoimmune destruction of islet beta cells, and that pregnancy via haploidentical male mates can delay the development of autoimmune diabetes in female NOD mice. The mechanism of this effect is unclear. This work forms part of the dissertation of Yannick Fuchs at the University of Technology Dresden and of Katharina Foertsch at the University of Technology Munich. Kerstin Adler received support from the NIH/DFG

Research Career Transition Award Program (KO 3418/1-1). Yannick Fuchs is supported by a grant from the BMBF to the DZD e.V. (FKZ01GI0924) and the DFG Research Center and Cluster of Excellence–Center for Regenerative Therapies Dresden (FZ 111). The authors

have nothing to declare. Fig. S1. Schematic representation of the study design. Litter-matched female non-obese diabetic (NOD) mice were mated to syngeneic NOD, Non-specific serine/threonine protein kinase major histocompatibility complex (MHC) haploidentical CByB6F1/J and fully mismatched C57BL/6J male mice at (a) 10 weeks and (b) 13 weeks of age. The number of females mated and the number of males used for mating are provided in parentheses. Unmated litter-matched female NOD mice were used as control groups. The total number of offspring and the number of NOD dams that had productive litters are also indicated. Fig. S2. Screening for fetal microchimeric cells in splenocytes from non-obese diabetic (NOD) dams after pregnancy from haploidentical CByB6F1/J mates. Fluorescence staining of major histocompatibility complex (MHC) H-2Kb (ordinate) molecules on CD4+ and CD8+ T cells was analysed by flow cytometry. The left column shows all viable cells additionally stained for H-2Db molecules. The column in the middle shows cells gated for CD4+, and the right column shows cells gated for CD8+. The numbers represent the percentage of H-2Kb-positive cells within the gated area of each graph. (a) To control the staining experiments, splenocytes of one C57BL/6J and one unmated NOD mouse were stained and analysed individually as well as in mixtures of 1:100 and 1:1000.