Contribution of antigen-presenting cells, airway epithelial cells and innate immune cells in controlling house dust mite specific T lymphocyte immunity

Asthma is a chronic inflammatory disease of the airways that is seen increasingly in westernalized countries. Airway dendritic cells (DC) and epithelial cells play a crucial role in the process of allergic sensitization to house dust mite (HDM), leading to asthma. Moreover, the recruitment of innate cells in the vicinity of DCs helps development of allergic inflammation. So far, HDM-specific T cell responses to HDM have never been studied due to the absence of any specific tools. To be able to address specific T cell activation to HDM, the host lab has successfully generated a new mouse line (1-Der mice) in which almost all T cells react to Der p 1, one of the major allergens of HDM. The specific objective of this project is to further characterize the immune response to HDM allergen inhalation. We will examine where and with what kinetics the HDMspecific T lymphocyte response occurs upon first or repeated encounter with HDM. We will analyze which antigen presenting cell (sub)population is presenting HDM allergen to T cells in vivo. Finally, the precise contribution of the epithelium and the innate cells on generation of HDM-specific T cell immunity will be addressed. Defining in more detail how T lymphocyte differentiation occurs in response to HDM might allow us to understand the influence of environmental and genetic risk factors on allergy. The ultimate goal is to halt harmful T cell responses to allergens.