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Airway hyperresponsiveness in mouse models of asthma is associated with activated T cells in the airways
Adoptive transfer of activated T cells has been shown to induce allergic responses in the lung, however, direct physiological evidence of whether these T cells home to the airways is lacking. This study aimed to determine the role of CD4+ T cells in the generation of airway hyperresponsiveness (AHR) in mouse models of asthma.
Methods: (1) 129/Sv, C57BL/6 and BALB/c mice were sensitized and challenged with ovalbumin (OVA). AHR, inflammatory cells, serum IgE and IgG1 and the number of CD4+CD69+ T cells in the trachea and peripheral lung were measured. (2) DO11.10 transgenic T cells that recognize OVA were transferred to naïve BALB/c recipients. Recipient mice were primed and challenged with OVA and assessed for AHR and serum antibodies. (3) Naïve BALB/c mice were passively sensitized with high titre IgE/IgG1 titre serum, challenged with OVA and assessed for AHR.
Results: (1) AHR to inhaled methacholine (MCh) was induced by OVA in BALB/c mice only. This correlated with the presence of CD4+CD69+ T cells and IgG1. (2) After 5 OVA challenges naïve BALB/c mice primed with DO11.10 T cells demonstrated AHR (p = 0.049) to MCh. (3) Passive transfer of high titre IgE/IgG1 serum did not result in AHR.
Conclusions: The presence of AHR in BALB/c mice was linked to the numbers of CD4+CD69+ T cells and IgG1. Adoptive transfer of T cells that recognize OVA resulted in AHR following challenge suggesting that these T cells traffic to the airway after challenge. This could not be replicated by passively sensitizing mice with high IgE/IgG1 titre serum alone. This study highlighted the potential role of CD4+ T cells in the development of AHR and further studies using this system may be able to dissect the mechanism by which this occurs.
Department/SchoolTasmanian School of Medicine
PublisherWiley-Blackwell Publishing Asia
Place of publicationAustralia
Event titleThoracic Society of Australia and New Zealand Annual Scientific Meeting 2008
Event VenueMelbourne, Australia
Date of Event (Start Date)2008-03-28
Date of Event (End Date)2008-03-31