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Notes: Background The role of antigen presenting cells (APC) in allergic rhinitis is underexposed. Allergen presentation to T lymphocytes is probably an important aspect of the pathophysiological mechanism of allergic rhinitis.Objectives The aim of the study was to investigate the presence and dynamics of APC with special emphasis on Langcrhans cells (LC) in the nasal mucosa of patients with an isolated grass pollen allergy during an out-of-season 2-week allergen exposure, mimicking the natural grass pollen season.Methods Seventeen patients with isolated grass pollen allergy and four control subjects were challenged daily with allergen during a 2-week period in the winter. Biopsy specimens were obtained once before, six times during and once after the provocation period. Biopsy sections were stained with monoclonal antibodies: OKT6 (CDla-Langerhans cells). Ki-M6 (CD68 macrophages), L25 (dendritic cells), anti-IgE, HLA-DR and HLA-DQ (Major Histoeompatibihty Complex Class II - antigen presenting eells), as well as staining with acid phosphatase.Results APC with different characteristics are present in the epithelium and lamina propria of the nasal mucosa. The number of LC increased significantly in epithelium and lamina propria. IgE+-LC were present in the nasal mucosa and increase during provocation, HLA-DR+ cells with dendritic and lymphocytic morphology and HLA-DQ+ cells were found. The number of these cells increased during provocation in epithelium and lamina propria. The number of HLA-DR+ epithelial cells did not change. A significant increase in the number of Ki-M6+ cells (macrophages) was found in the lamina propria. However, Ki-M6+ cells increased to the same extent in the lamina propria in the control group.Conclusion APC are influenced by allergen provocation. This study supports the hypothesis that (IgE+) LC are involved in allergic rhinitis. The role macrophages play remains doubtful.

Notes: Mast cell degranulation is thought to be an important component of the pathogenesis of allergic rhinitis. Quantitative studies on mast cells in nasal mucosa after allergen exposure have given widely divergent results, ranging from an overall decrease via redistribution to an overall increase. We investigated this problem by employing a combination of anti-IgE and toluidine blue staining of biopsy specimens. In allergic patients anti-IgE was found to identify all mast cells and toluidine blue to detect mast cells that were not (totally) degranulated.The study was composed of two parts done in different patient groups. In the first part of the study biopsies were performed in 23 patients with isolated grass-pollen allergy, once during natural provocation in the summer and once in the winter. Biopsies were also performed in 12 controls. Non-allergic controls were found to have the same number of mast cells in the lamina propria as asymptomatic allergic patients. The controls seldom have mast cells in the epithelium. The patients with isolated grass-pollen allergy showed an increase in the numbers of mast cells in the lamina propria during natural provocation and the same seemed to occur in the epithelium as well. During natural provocation almost all of the mast cells in the epithelium and half of those in the lamina propria were degranulated.In the second part of the study 17 patients with isolated grass-pollen allergy and four controls were challenged daily with allergen extract during a 2-week period in the winter. During this period biopsies were performed at eight different occasions, i.e. once before, six occasions during and once after the provocation period. The results of this part of the study showed that during provocation mast cells migrate to the surface of the nasal mucosa, where they become degranulated, and that the pool of mast cells in the lamina propria was apparently replenished by migration of mast cells from the vessels in the lamina propria. The total number of mast cells in the lamina propria remained approximately the same while the mast cells residing in an increasingly thick layer measured from the basal membrane into the lamina propria became degranulated. After 2 weeks, 82% of the mast cells in the lamina propria was degranulated and it was only in the deepest layers that some toluidine blue positive cells were found.This study can explain the seemingly conflicting reports in the literature on mast cell dynamics and degranulation and shows that the reported differences are due to differences in the techniques used and the time of evaluation.

Notes: Topical corticosteroids have proved to be effective in the treatment of allergic rhinitis. The symptomatology of allergic rhinitis is considered to be the result of the accumulation and activation of inflammatory cells and cytokine release and hence the efficacy of corticosteroids is associated with their anti-inflammatory action. New advances in allergic inflammation now suggest that not only mast cells and eosinophils but also T-lymphocytes and antigen-presenting dendritic cells, play an important role in the inflammatory reaction. The effect of topical fluticasone propionate on cellular infiltration in the nasal mucosa is examined, with an emphasis on two studies performed in Rotterdam, The Netherlands. The cells influenced most by corticosteroid therapy were Langerhans' cells (antigen-presenting cells), which were almost completely eradicated, possibly resulting in diminished antigen presentation, and eosinophils. There was a reduction in the number of epithelial mast cells, but the number of T-lymphocytes only decreased following high doses of corticosteroid therapy or long-term treatment. However, T-lymphocyte function was influenced, as shown by the reduction in the T-helper, (ThJ-related cytokines, interleukin (1L)-4 and IL-5. Topical corticosteroid therapy had no effect on the accumulation of macrophages. The reduction in antigen presentation, and the decrease in T-lymphocyte stimulation and cytokine production, may cause a reduced influx of eosinophils and other inflammatory cells, resulting in diminished symptomatology.

Notes: Mast cell degranulation, and the subsequent recruitment of infiltrating inflammatory cells, such as eosinophils, into the nasal mucosa has long been considered the most important model to explain allergic rhinitis. Several studies show a decrease in the number of eosinophils and possibly also mast cells during local corticosteroid treatment. Over the last decade, a new model to explain allergic inflammation has evolved. In this model, Langerhans’cells and T-cells play an important role. Langerhans’cells possess a high affinity receptor for IgE. In patients with allergic rhinitis, allergen provocation results in stimulation of T-cells by the IgE-positive Langerhans’cells. The T-cells produce a number of cytokines which stimulate IgE production as well as the inflammatory reaction. The number of T-cells is not usually influenced by corticosteroid treatment; however, the function of the T-cells, shown by the spectrum of cytokines produced, is clearly influenced. The cells that are most dramatically affected by local corticosteroid treatment are the Langerhans’cells, which completely disappear during treatment. This decrease suggests that there is a reduction in antigen presentation. The subsequent decrease in T-cell stimulation may result in a reduction of the reactions that are dependent on T-cell-derived mediators.

Notes: The effect of nasal corticosteroid therapy on allergic rhinitis is uncertain. In a double-blind, placebo-controlled study over 3 months, we investigated the influence of a new corticosteroid spray, fluticasone propionate aqueous nasal spray (FPANS), on Langerhans cells (CD1a+ cells), HLA-DR+ cells, and T cells in nasal mucosa. Efficacy was evaluated by nasal symptom score. This treatment significantly decreased the number of CDla+ cells and HLA-DR+ cells in the nasal mucosa. Furthermore, a clear trend of decreasing numbers of T cells in nasal epithelium was found. No change in nasal symptom score was found after the treatment period. These findings suggest that fluticasone propionate aqueous nasal spray decreases the antigen presentation in nasal allergy.

Notes: Mast cells in the nasal mucosa can be studied by means of monoclonal antibodies (mAb) against tryptase (T+MC) and chymase (C+MC). Fixation with acetone gives more positive cells than does fixation with Carnoy's fluid. In frozen biopsy specimens of allergic nasal mucosa fixed with acetone, the number of T+MC equals that of C+MC. When fixed with Carnoy's fluid, however, the number of T+MC is larger than the number of C+MC. The decrease in both T+MC and C+MC resulting from fixation with Carnoy's fluid is time-related and depends on the type of mAb used. Carnoy fixation time gives a decrease in the number of C+MC within 1 min, whereas the number of T+MC decreases only after 10 min. Within 1 min, the number of C+MC decreases to a level where continued fixation no longer gives further decreases in the number of cells. Two populations of mast cells can be distinguished here: one sensitive and the other insensitive to Carnoy's fluid. When double-staining is used, fixation with acetone gives three populations of mast cells: one positive for tryptase (T+C-MC), another positive for tryptase and chymase (T+C+MC), and a third one positive for chymase (T-C+MC). These three populations were found in lymph node, spleen, thymus, dermis, lung parenchyma, small intestinal submucosa, and nasal mucosa.