Immunotherapy of allergic disease

Allergic disease is due to the inappropriate activation of CD4+ T cells responding to environmental allergens that are ingested, inhaled, or that contact the skin. We have shown in a mouse model that allergen-specific CTL can ameliorate allergic airway inflammation, apparently by killing the airway dendritic cells that cause activation of disease-mediating CD4+ T cells in the airway. Here we propose to establish whether the protective effects of CTL on allergic inflammation also extend to other tissues frequently affected by allergic disease. We will establish mouse models of allergic disease in skin and intestinal tract, examine the role of dendritic cells in promoting allergic inflammation in these tissues, and test whether allergen-specific CTL can reduce relevant manifestations of disease. These results may form the basis of allergen-specific treatments of inflammatory allergic disease. They may also help explain why exposure to allergens causes the development of allergies in only some individuals.