Cat allergen sensitivity in HLA DR1-transgenic mice A model to investigate mechanisms of prophylactic allergen tolerance

RationaleIn order to determine cellular and molecular mechanisms of tolerance to cat allergen Feld1, we have developed a model of peptide-induced prophylactic tolerance in cat allergen sensitized HLA DRB1∗ 0101 transgenic mice using a DR1-restricted Feld1 peptide which is tolerogenic in humans.MethodsMice received intradermal injections of DR1-restricted Feld1 peptide 4 (P4) or influenza hemagglutinin peptide (HA) as a control. Two weeks later, pulmonary inflammation was established by sensitization with Feld1 in alum (3X i.p.) followed by intra-nasal challenge with cat allergen prior to sacrifice.ResultsP4 pre-treatment at a range of doses reduced airway hyperreactivity to 30 mg/ml aerosolized methacholine by up to 40% compared to corresponding HA pre-treated control mice. P4 pre-treated mice also demonstrated reduced peribronchial and perivascular inflammation in the lung. In addition, these mice had consistently lower levels of the Th2 cytokines IL-4, IL-5 and IL-13 in both bronchoalveolar lavage and homogenized lung tissue compared to HA controls.ConclusionsPre-treatment with Feld1 P4 downregulated subsequent cat allergen-induced inflammatory responses in DR1 transgenic mice, demonstrating a novel model system in which to elucidate mechanisms controlling HLA-restricted peptide-induced tolerance in human allergy.