Cytotoxic T lymphocyte-mediated immunotherapy of allergic airway inflammation

Asthma is an inflammatory allergic disease due to the inappropriate activation of airway CD4+ T cells to inhaled allergens. We have used a mouse model to show that allergen-specific CTL can ameliorate allergic airway inflammation, apparently by killing the airway dendritic cells that present allergen to disease-mediating CD4+ T cells in the airway and cause their activation. Here we propose to further characterize the potential of allergen-specific CTL to inhibit established allergic airway inflammation by using a model of chronic disease that more closely resembles the human situation. The mechanism of CTL therapy, and its effects on airway inflammation and CD4+ T cell memory will be established and compared to steroid treatment, the current therapy for asthma. These results may form the basis of allergen-specific treatments of allergic airway disease. They may also help explain why exposure to allergens causes the development of allergy and asthma in only some individuals.