Dendritic cells in asthma: a function beyond sensitization

textabstractThe aim of this thesis is to characterize the involvement of dendritic cells in the induction and maintenance of the secondary immune response leading to an eosinophilic airway inflammation as seen in asthma. Special attention was attributed to the mechanisms by which these cells accumulate in the airways of challenged mice, to their interaction with primed CD4+ T cells as well as to their functional contribution to primed T cell activation. These questions were addressed in a well-established murine model of eosinophilic airway inflammation Balb/c mice were sensitized to OVA by an intratracheal injection of OVA-pulsed bone marrow-derived DCs. Ten days post-sensitization, mice were challenged with an aerosol of the same antigen resulting in an eosinophilic airway inflammation as shown by histological analysis of lungs revealing peribronchial and perivascular inflammatory infiltrates and goblet cell hyperplasia, increased numbers of eosinophils in bronchoalveolar lavage fluid and Th2 cytokine production by draining lymph nodes of the lung. To determine the role of the dendritic cell in the secondary immune response to inhaled allergen the following research questions were addressed in this thesis using a murine model for asthma: - Does the number of dendritic cells in the airways increase during a secondary immune response? (Chapter 4) - Is an intratracheal injection of antigen pulsed dendritic cells sufficient to induce a secondary immune response in already sensitized mice? (Chapter 5 en 6) - Does depletion of dendritic cells in sensitized mice before and during challenge inhibit the development of an eosinophilic airway inflammation? (Chapter 5) - Does the capacity of dendritic cells to provide CDS0/86 costimulation contribute to the function of dendritic cells in the secondary immune response? (Chapter 6) - Do eosinophils play a role as antigen presenting cells during the secondary immune response? (Chapter 7