- BACKGROUND: Treatment of patients with cat allergy with peptides derived from Fel d 1 (the major cat allergen) ameliorated symptoms of cat allergy in phase 2 clinical trials. OBJECTIVE: We sought to demonstrate that the tolerance induced by Fel d 1 peptide immunotherapy can be exploited to reduce allergic responses to a second allergen, ovalbumin (OVA), in mice sensitized dually to OVA and Fel d 1. METHODS: Induction of tolerance to OVA was achieved through simultaneous exposure to both allergens after peptide treatment. Functional tolerance to each allergen was assessed in a model of allergic airways disease in which treated mice were protected from eosinophilia, goblet cell hyperplasia, and TH2 cell infiltration. RESULTS: Suppression of allergic responses to cat allergen challenge was associated with significant increases in numbers of CD4+CD25+Foxp3+ T cells, IL-10+ cells, and CD19+IL-10+ B cells, whereas the response to OVA was associated with a marked reduction in numbers of TH2 cytokine-secreting T cells and less prominent changes in outcomes associated with immune regulation. CONCLUSIONS: These observations suggest that immune tolerance induced by peptide immunotherapy can be used experimentally to treat an allergic response to another allergen and that the molecular mechanisms underlying induction of tolerance to a treatment-specific allergen and a bystander allergen might be different.