The pathogenesis of allergic rhinitis : cellular aspects with special emphasis on Langerhans cells

Present ideas concerning the pathogenesis of allergic rhinitis are largely deduced from systemic investigations and extrapolated from studies in the skin and the lung. Studies on allergic rhinitis generally comprise clinical aspects and/or biochemical, humoral and cellular features of the epithelial surface and the nasal secretions. little is known about what happens in the nasal mucosa itself. The aim of the investigations, described in this thesis, was to investigate the cellular aspects of the pathogenesis of allergic rhinitis using immunohistochemical staining techniques in biopsy specimens of nasal mucosa. A biopsy method was developed, which can be repeated several times (chapter 4). Biopsy specimens of nasal mucosa of patients with allergic rhinitis and nonallergic controls were studied to broadly characterize and quantitate the cellular infiltrates (chapter 5 and 7). Mast cell dynamics and degranulation were studied in an allergen provocation study out of the grass-pollen season (chapter 6). Although mast cell degranulation has long time been considered to be the proper model to explain allergic rhinitis, the findings described in the first part of this thesis, suggest that other cell types, particularly antigen presenting cells and T cells, are involved as well. The antigen presenting cells were further characterized and their contact with other cell types was evaluated (chapter 8). The dynamics and the behaviour of these cells in the nasal mucosa of patients with isolated grass-pollen allergy were studied in biopsy specimens taken before, during and after natural provocation (chapter 9) and during allergen provocation studies outside the grass-pollen season (chapter 1 0 and 11). Finally the effect of treatment with the nasal corticosteroid spray Fluticasone on antigen-presenting cells, and especially the langerhans cell was studied (chapter 12).