The 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