To test our hypothesis,

we crossed MUC1 transgenic mice, which express human MUC1 under the endogenous promoter, with the loxP-Stop-loxP-KraS(G12D/+) (Kras) mice, in which endometriosis can be induced through Cre-loxP recombination. The double transgenic MUC1 Kras mice develop benign, MUC1-positive ovarian lesions, closely resembling human endometriosis. Subsequent to disease induction, the mice generate high titers of IgM and IgG antibodies that are specific Caspase-dependent apoptosis for MUC1. Antibodies appear early in disease and the predominance of the IgG1 subclass suggests Th2-driven immunity. Immune phenotyping revealed an accumulation of Foxp3+ CD4 regulatory T cells (Tregs) in the draining lymph nodes at selleck chemicals late-stage disease. Furthermore, our observations in human endometriosis showed a similar recruitment of FOXP3+ CD4 T cells. Overall, our results reveal a Th2/Treg-dominant natural immunity in endometriosis with potential implications

for cancer progression.”
“Objectives: To determine the prophylactic efficacy of an Sm-p80-based vaccine formulation against challenge infection with Schistosoma mansoni in mice using an approach comprising of initial priming with DNA and boosting with recombinant protein in the presence of resiquimod (R848) as an adjuvant.

Methods: In the first experiment (prime-boost approach), mice were primed with Sm-p80-pcDNA3 (week 0) and boosted at weeks 4 and 8 with recombinant Sm-p80 formulated in resiquimod (R848). Each learn more mouse in the control group first received only pcDNA3 and was boosted with R848. In the second set of experiments (recombinant protein approach), mice were immunized (week 0) and boosted (weeks 4 and 8) with rSm-p80 formulated in R848. Animals of the control group in this series of experiments received only R848 at 0, 4, and 8 weeks. All of the animals from both the ‘prime-boost’ and ‘recombinant protein’ groups were challenged with cercariae of S. mansoni, 4 weeks after the last immunization. The mice were sacrificed 6 weeks post-challenge and the reductions in worm burden and egg production were determined. Sm-p80-specific antibody titers were

estimated in the mice sera by ELISA. Cytokine mRNA and protein production by proliferating splenocytes in response to in vitro stimulation with Sm-p80, were estimated via RT-PCR and ELISA, respectively.

Results: Vaccination with Sm-p80 (prime-boost approach) showed 49% reduction in worm burden; with the recombinant protein approach the protection was found to be 50%. The protection levels were correlated with antibody production. Upon antigenic stimulation with recombinant Sm-p80, splenocytes secreted significant levels of interferon (IFN)-gamma and interleukin (IL)-2, indicating that the immune responses were Th1-biased and this was further supported in terms of distribution of antibody isotypes and mRNA expression of cytokines.