Allergen-induced IgE-dependent gut inflammation in a human PBMC-engrafted murine model of allergy.

BACKGROUND: Humanized murine models comprise a new tool to analyze novel therapeutic strategies for allergic diseases of the intestine.¦OBJECTIVE: In this study we developed a human PBMC-engrafted murine model of allergen-driven gut inflammation and analyzed the underlying immunologic mechanisms.¦METHODS: Nonobese diabetic (NOD)-scid-γc(-/-) mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or not. Three weeks later, mice were challenged with the allergen orally or rectally, and gut inflammation was monitored with a high-resolution video miniendoscopic system, as well as histologically.¦RESULTS: Using the aeroallergens birch or grass pollen as model allergens and, for some donors, also hazelnut allergen, we show that allergen-specific human IgE in murine sera and allergen-specific proliferation and cytokine production of human CD4(+) T cells recovered from spleens after 3 weeks could only be measured in mice treated with PBMCs plus allergen. Importantly, these mice had the highest endoscopic scores evaluating translucent structure, granularity, fibrin, vascularity, and stool after oral or rectal allergen challenge and a strong histologic inflammation of the colon. Analyzing the underlying mechanisms, we demonstrate that allergen-associated colitis was dependent on IgE, human IgE receptor-expressing effector cells, and the mediators histamine and platelet-activating factor.¦CONCLUSION: These results demonstrate that allergic gut inflammation can be induced in human PBMC-engrafted mice, allowing the investigation of pathophysiologic mechanisms of allergic diseases of the intestine and evaluation of therapeutic interventions

Polarized inelastic neutron scattering of the partially ordered Tb2Sn2O7

We present inelastic neutron scattering results on the geometrically frustrated pyrochlore Tb2Sn2O7. At high temperature T gt;50K, this system resembles the cooperative paramagnet Tb2Ti2O7, while at low temperature T 60mK, it displays remarkably different behavior. Powder neutron scattering, susceptibility and specific heat techniques have shown that below 0.87K Tb2Sn2O7 enters a partially ordered state that is characterized by two sublattice ferrimagnetic long range order which coexists with paramagnetic spin components. We show that i the low temperature state produces a large internal field and collective excitations and ii the coexisting paramagnetic state persists down to 0.1K, with spins fluctuation at a rate greater than 0.04 THz, resulting in a diffuse magnetic background to the diffraction patterns. A low lying excitation at 1.2meV partially softens as short range correlations build up while cooling in the paramagnetic stat