Physiological and immunological responses to allergen in three strains of mouse

Background: Asthma is a chronic inflammatory disease of the airways characterised by airway hyperresponsiveness (AHR) and reversible airway obstruction. Airway and lung eosinophilia and CD4+ T cells (which express a Th2 pattern of cytokines) are believed to play pivotal roles in the development of allergic asthma.

Aim: To determine the relationship of CD4+ T cells to AHR in low, medium and high IgE responder strains of mice.

Methods: Female BALB/c, C57BL/6J and 129/Sv mice were systemically sensitised with ovalbumin (OVA) adsorbed onto Alum and challenged with an OVA or control (saline) aerosol. 24 hrs later anaesthetised, tracheostomised and ventilated mice were assessed for AHR to inhaled methacholine (MCh) using the low frequency forced oscillation technique in order to measure changes in airway resistance, tissue damping and tissue elastance. Bronchoalveolar lavage (BAL) and sera were used to assess inflammation and antibodies respectively. Fluorescence-activated cell-sorting (FACS) was used to assess the presence and activation status of CD4+ T cells in the airways 12 hrs after OVA or saline challenge.

Results: AHR to MCh was induced by 1 OVA aerosol in BALB/c mice, but not in C57BL/6J or 129/Sv mice. 129/Sv mice exhibited significantly increased total cells, eosinophilia and serum IgE when exposed to 1 OVA aerosol compared to BALB/c or C57BL/6J mice. Numbers of activated Tcells in the airways were increased in BALB/c mice compared to the other two strains.

Conclusion: The same sensitisation and allergen challenge protocol applied to murine strains producing differing Th2 profiles results in markedly different patterns of physiological and immunological responses.