['Allergic reactions to tree nuts are often severe and are outgrown in less than 10% of diagnosed patients.', 'To determine whether treatment of underlying tree nut sensitization will prevent allergic reactions to cross-reacting tree nuts and to determine the effects of single-tree nut immunotherapy on true multi-tree nut sensitization.', 'Cross-reactivity model: Cashew-sensitized mice underwent immunotherapy with cashew and were subsequently challenged with cashew and pistachio. Multisensitization model: Cashew plus walnut-sensitized mice were treated with cashew alone, walnut alone, or both cashew and walnut and then underwent challenges to cashew and walnut. Challenges were assessed on the basis of symptoms, changes in body temperature, and mouse mast cell protease-1 release.', 'In the cross-reactivity model, cashew immunotherapy completely prevented allergic reactions on challenges with cashew or the cross-reactive pistachio. In the multisensitization model, mice with cashew plus walnut allergy were significantly protected from anaphylactic reactions on cashew challenge in both the cashew-alone and walnut-alone immunotherapy groups. Results from the walnut challenge demonstrated significantly decreased allergic responses in the walnut immunotherapy group, whereas mice in the cashew immunotherapy group experienced significantly lower symptoms. In the cross-reactivity model, immunotherapy effectively decreased IL-4 and IL-5 production and increased IL-12 relative to placebo while also inducing a 5-fold increase in specific IgG(1).'] Does single-tree nut immunotherapy attenuate allergic reactions in mice with hypersensitivity to multiple tree nuts?