Regulatory cells and dendritic cells can attenuate allergen-induced airway hyperresponsiveness

Airway hyperresponsiveness (AHR) is one of the primary features of allergic airways disease. HowAHR is limited in the face of continued allergen exposure in asthmatic individuals remains unclear. The aim of this study was to examine the role of airway CD4+ T cells and Dendritic Cells (DC) in initiation and subsequent attenuation of AHR. BALB/c mice were sensitized with intraperitoneal ovalbumin (OVA) in Aluminium Hydroxide and challenged with a single or 3-weeks of OVA aerosol. One OVA aerosol induced AHR to methacholine (MCh), as measured by low-frequency forced oscillation technique, whilst multiple challenges resulted in attenuation of MCh responses. Similar proportions of CD4+ T cells became activated following both aerosol regimes, however total numbers of airway CD4+ T cells were significantly decreased, and OVA-specific CD4+ T cell proliferation in draining lymph nodes was significantly reduced after multiple versus one OVA aerosol. Analysis of antigen handling by airwayAntigen Presenting Cell populations showed antigen uptake (OVA-647) and processing (DQ-OVA) by macrophages and airway DC subsets to be down-regulated after 3-weeks of OVA aerosols. Furthermore, multiple challenges resulted in a marked increase in CD4+ 25hifoxP3+ cells (T regulatory cells) within the trachea when compared with a single challenge. In addition, adoptive transfer of 1X10 6 T regulatory cells taken from thoracic draining lymph nodes of multiple-challenged mice suppressed AHR in single-OVA recipients and T regulatory cell depletion restored AHR in vivo. These data suggest that multiple inhaled OVAchallenges altered the function of airway DC, resulting in reduced antigen uptake and processing, leading to limited CD4+ T cell proliferation and/or recruitment to the airways. Furthermore these data show that administration of T regulatory cells suppressed AHR in established airways disease.