Kleinjan, A.

Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis (Article)

2012-01-01T00:00:00Z

Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Although the aetiology is unknown, sarcoidosis is thought to be mediated by Th1 lymphocytes. Recently, IL-17A has been implicated in granuloma formation in various diseases, including tuberculosis. Therefore, we hypothesized that Th17 cells play a role in sarcoidosis, paralleling recent findings in autoimmune diseases such as RA. The aim of our study was to investigate the role of Th17 cells in sarcoidosis. T cells were investigated by intracellular flow cytometry and immunohistochemistry, in blood, bronchoalveolar lavages (BALs) and bronchial mucosal biopsies from a cohort of newly diagnosed sarcoidosis patients and healthy controls. Circulating memory CD4(+) T-cell populations of sarcoidosis patients contained significantly increased proportions of IL-17A(+) cells when compared with healthy controls. Interestingly, proportions of IL-17A/IFN-γ and IL-17A/IL-4 double-producing cells were significantly increased in blood of sarcoidosis patients and were present in substantial numbers in BAL. In granuloma-containing, but not in non-granulomatous sarcoidosis biopsies, we found significantly increased numbers of IL-17A(+) T cells, located in and around granulomas throughout the lamina propria. IL-22(+) T cells were increased in the subepithelial layer. Enhanced IL-17A expression in granulomas and the presence of IL-17A(+), IL-17A(+)IFN-γ(+) and IL-17A(+)IL-4(+)memory Th cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction or maintenance in sarcoidosis. Therefore, neutralization of IL-17A activity may be a novel strategy to treat sarcoidosis.

Nonsteroidal anti-inflammatory drugs do not interfere with imiquimod treatment for usual type vulvar intraepithelial neoplasia (Article)

2011-05-01T00:00:00Z

Imiquimod has been shown to be an effective treatment for usual type vulvar intraepithelial neoplasia (uVIN). Since local inflammation and burning are common side effects, patients often use nonsteroidal anti-inflammatory drugs (NSAIDs). Our study investigated whether NSAID-use, which has been documented to inhibit the cell-mediated immune response, interferes with the outcome of imiquimod treatment. Monocyte-derived dendritic cells (moDCs) and Langerhans cells (moLCs) were cultured in the presence of NSAIDs. The expression of relevant surface markers (CD80, CD86, CD40, HLA-DR, CCR6 and CCR7), stimulatory function, and cytokine production were evaluated. Furthermore, we analyzed in uVIN patients whether frequent NSAID-use had an effect on the clinical response and on immunocompetent cell counts before and after imiquimod treatment. Although an effect was observed on the expression of moDC and moLC maturation markers, NSAIDs did not affect the ability of moDCs and moLCs to stimulate allogeneic T-cell proliferation, or the production of cytokines in an allogeneic T-cell stimulation assay. In agreement with this, in uVIN patients treated with imiquimod, no interference of frequent NSAID-use with clinical outcome was observed. However, we did notice that high CD1a+and CD207+cell counts in frequent NSAID-users before treatment seemed to predict a favourable response to imiquimod treatment. Our data indicate that NSAID-use does not seem to interfere with moDC and moLC function and does not interfere with immunomodulatory properties of imiquimod in uVIN patients. Therefore, NSAIDs can safely be used to reduce imiquimod side effects in uVIN patients during treatment. Copyright

The crucial role of dendritic cells in rhinitis (Article)

2011-02-01T00:00:00Z

Purpose of Review: Dendritic cells generally play an important role as sentinels in the immune system. They are also very important in protecting the airways from invading pathogens and harmful particles and antigens. This review discusses current knowledge about dendritic cell function and the interaction between dendritic cells and their surroundings, the epithelium, during their presence in the nasal mucosa. Recent Findings: There are some phenotypical differences between myeloid dendritic cells and plasmacytoid dendritic cells in different types of rhinitis. Since it has become possible to perform functional studies on purified dendritic cell populations obtained from the upper airway mucosa, a number of studies have appeared. Some confirm that thymic stromal lymphopoietin is present in the nasal mucosa and that it may influence dendritic cell-T-cell interaction in a pro-Th2 way. Epithelial cells share several characteristics with dendritic cells, but they cannot migrate and move antigens to draining lymph nodes. Summary: Several functional dendritic cell studies have been published indicating that there are disease-dependent dendritic cell differences in rhinitis. In addition to these differences, factors like epithelial cells and T cells influence dendritic cells. Several new therapeutic options are available targeting direct or indirect dendritic cell functions.

Imiquimod-induced clearance of HPV is associated with normalization of immune cell counts in usual type vulvar intraepithelial neoplasia (Article)

2010-12-15T00:00:00Z

Recently, we reported on the efficacy of imiquimod for treatment of usual type vulvar intraepithelial neoplasia (uVIN). A histologic regression of uVIN to normal tissue was observed in 58% of patients. As success of treatment is related to clearance of high-risk human papilloma virus (HPV), the aim of our study was to assess differences in immune cell counts and in the expression of p16INK4a in VIN tissue before and after imiquimod treatment, in relation to HPV clearance and clinical response. Vulvar tissue samples taken prior to imiquimod treatment and 4 weeks after treatment were tested for the presence of HPV. Previously determined immune cell counts (CD1a, CD207, CD208, CD123/CD11c, CD94, CD4, CD8 and CD25/HLA-DR) in epidermis and dermis of 25 VIN patients and 19 healthy controls were completed with the counts for CD14 and CD68. The expression of p16INK4a was investigated by immunohistochemistry in 15 patients. Before imiquimod treatment, both HPV cleared and HPV noncleared patients showed mainly in the dermis significantly upregulated immune cell counts compared to healthy controls. However, in patients that cleared HPV and showed histologic regression already 4 weeks after imiquimod treatment, immune cell counts and p16INK4a expression were normalized. In conclusion, our data indicate that imiquimod-induced clearance of HPV results in normalization of counts for certain immune cells and is strongly correlated with histologic regression of the disease.

United airways: Circulating Th2 effector cells in an allergic rhinitis model are responsible for promoting lower airways inflammation (Article)

2010-03-01T00:00:00Z

Background Allergic rhinitis (AR) and asthma often coexist and are referred to as 'united airways' disease. However, the molecular and cellular pathways that are crucially involved in the interaction between upper and lower airways remain to be identified. Objective We sought to assess whether and how AR exacerbates lower airway inflammation upon allergen challenge in mice. Methods We previously developed an intranasal ovalbumin (OVA)-driven AR model, characterized by nasal eosinophilic inflammation, enhanced serum levels of OVA-specific IgE and Th2 cytokine production in cervical lymph nodes. In OVA-sensitized mice with or without AR, a lower airway challenge was given, and after 24 h, lower airway inflammation was analysed. Results We found that AR mice were more susceptible to eosinophilic inflammation following a lower airway OVA challenge than OVA-sensitized controls. AR mice manifested increased numbers of eosinophils in bronchoalveolar lavage fluid and increased inter-cellular adhesion molecule-1 (ICAM-1) expression on lung endothelium, when compared with OVA-sensitized controls. Depletion of T cells in OVA-challenged AR mice completely abrogated all hallmarks of lower airway inflammation, including enhanced IL-5 and tissue eosinophilia. Conversely, adoptive transfer of Th2 effector cells in naïve animals induced lower airway eosinophilic inflammation after challenge with OVA. Blocking T cell recirculation during AR development by the spingosine-1 analogue FTY720 also prevented lower airway inflammation including ICAM-1 expression in AR mice upon a single lower airway challenge. Conclusion Our mouse model of 'united airways' disease supports epidemiological and clinical data that AR has a significant impact on lower airway inflammation. Circulating Th2 effector cells are responsible for lung priming in AR mice, most likely through up-regulation of ICAM-1.

A novel method for isolating dendritic cells from human bronchoalveolar lavage fluid (Article)

2009-12-31T00:00:00Z

Background: Dendritic cells (DCs) play a pivotal role in linking the innate and adaptive immune response and have been implicated in a variety of pulmonary diseases. Currently, studies on the role of DCs are limited by difficulties in isolating DCs from the lung. Surgical lung specimens are not readily available and purification of DCs from digested lung tissue is likely to induce phenotypical and functional changes. DCs obtained from the alveolar spaces are thought to represent the local microenvironment and can be obtained using minimally invasive techniques. We developed a novel method of isolating DCs from bronchoalveolar lavage (BAL) fluid. Methods: After removal of macrophages, the remaining BAL cells were stained with a lineage mix (CD3-, CD14-, CD16-, CD19-, CD56-FITC), CD11c and HLA-DR and sorted with a FACS ARIA. DAPI was used as a dead-live marker. mDCs were low autofluorescent, lineage mix negative, CD11c+and HLA-DR+cells. pDCs were CD11c-but CD123+. Morphological assessment of sorted mDCs and pDCs was performed. Sorted mDCs were tested in a mixed leukocyte reaction (MLR) with naive CD4+T cells and evaluated for T cell differentiation and cytokine production. With confocal microscopy DC-T cell interaction was assessed. Results: Using our sorting strategy, mDCs and pDCs, with a high purity upon FACS analysis of the sorted fraction, were obtained. These cells showed the morphological characteristics of DCs. Most importantly, mDCs were able to induce T cell proliferation and differentiation in a MLR, and interact with T cells as assessed by confocal microscopy. These results indicate the presence of functional DCs. Freezing and thawing of the BAL cells did not affect phenotype or T cell stimulatory capacity of the isolated DCs. Conclusion: Using a novel sorting strategy, functional mDCs can be isolated from BAL fluid, enabling a detailed study in pulmonary disease.

Neuron-interacting satellite glial cells in human trigeminal ganglia have an APC phenotype (Article)

2009-08-15T00:00:00Z

Satellite glial cells (SGC) in sensory ganglia tightly envelop the neuronal cell body to form discrete anatomical units. This type of glial cell is considered neuroectoderm-derived and provides physical support to neuron somata. There are scattered hints in the literature suggesting that SGC have an immune-related function within sensory ganglia. In this study, we addressed the hypothesis that SGC are tissue-resident APC. The immune phenotype and function of a large series (n = 40) of human trigeminal ganglia (TG) were assessed by detailed flow cytometry, in situ analyses, and functional in vitro assays. Human TG-resident SGC (TG-SGC) uniformly expressed the common leukocyte marker CD45, albeit at lower levels compared with infiltrating T cells, and the macrophage markers CD14, CD68, and CD11b. In addition, TG-SGC expressed the myeloid dendritic cell (DC) marker CD11c, the T cell costimulatory molecules CD40, CD54, CD80, and CD86 and MHC class II. However, the mature DC marker CD83 was absent on TG-SGC. Functionally, TG-SGC phagocytosed fluorescent bacteria, but were unable to induce an allogeneic MLR. Finally, TG-infiltrating T cells expressed the T cell inhibitory molecules CD94/NKG2A and PD-1, and the interacting TG-SGC expressed the cognate ligands HLA-E and PD-L1, respectively. In conclusion, the data demonstrate that human TG-SGC have a unique leukocyte phenotype, with features of both macrophages and immature myeloid DC, indicating that they have a role as TG-resident APC with potential T cell modulatory properties. Copyright

Inducible costimulator blockade prolongs airway luminal patency in a mouse model of obliterative bronchiolitis (Article)

2008-11-27T00:00:00Z

BACKGROUND.: In human lung transplantation, chronic rejection is accompanied by obliterative bronchiolitis (OB), a fibrosing inflammatory condition that leads to occlusion of the bronchial lumen and graft failure. The pathogenesis of this disorder is poorly understood, but likely involves antigen presentation by dendritic cells (DC). We studied the presence and activation status of DCs in transplanted tracheas in a mouse model of OB and studied the effect on graft luminal patency of blocking the costimulatory B7RP-1/inducible costimulator (ICOS) pathway. METHODS.: Tracheas from Balb/C or from C57Bl/6 mice were transplanted heterotopically under the dorsal skin of C57Bl/6 mice. Histologic, fluorescence-activated cell sorter, and quantitative-polymerase chain reaction analyses were performed after 1, 2, or 4 weeks. In some groups, treatment with blocking rat anti-mICOS antibodies or irrelevant rat immunoglobulin G was administered during the entire observation period. RESULTS.: After heterotopic transplantation, both CD103CD11b and CD103CD11bMHC IIDCs accumulated in the airway epithelium as early as 1 week after allogeneic (mismatched) but not syngeneic (matched) transplantation. Four weeks after Tx, infiltration with CD11c MHCIIDCs and CD8 lymphocytes, luminal fibrosis and epithelial damage were more pronounced in the allogeneic than in the syngeneic setting. There was a 10-fold up-regulation of ICOS mRNA and of chemokines involved in T-cell influx in the mismatched setting compared with the matched setting. Strikingly, anti-ICOS treatment without other immunosuppression prevented luminal fibrosis in mismatched transplants. CONCLUSIONS.: Our results suggest that early infiltration by DC occurs in posttransplant OB. Blocking critical costimulatory molecules expressed on DCs, as in the B7RP1-ICOS pathway, prevents epithelial damage and luminal fibrosis.

Disturbed patterns of immunocompetent cells in usual-type vulvar intraepithelial neoplasia (Article)

2008-08-15T00:00:00Z

Genital infection with human papillomavirus (HPV) is usually transient, as the immune system is capable of eliminating the virus. When immunity "fails" and the infection persists, vulvar intraepithelial neoplasia (VIN) may develop. In this study, we examined the distribution of inflammatory cells in 51 patients with HPV-associated usual-type VIN and in 19 healthy controls. Frozen vulvar tissue samples were tested for the presence of HPV-DNA, and immunohistochemical staining for the markers CD1a, CD207, CD208, CD123/CD11c, CD94, CD4, CD8, and CD25/HLA-DR was performed. Cells were counted in both the epidermis and dermis over at least 2 mm of basal membrane length. In the epidermis of VIN patients, CDla+ and CD207+ (Langerin) dendritic cells (DC) and CD8+ T cells were significantly lower than in controls, whereas the number of CD123+/CD11c - plasmacytoid DCs (pDC) was significantly increased. No significant changes were observed for CD208+ DCs, CD94+ natural killer (NK) cells, CD4+ T cells, and CD25+/HLA-DR+ regulatory T cells. In the dermis of VIN patients, elevated numbers of CD208+, CD123+/CD11c-, CD94+, CD4+, CD8+, and CD25+/HLA-DR+ cells were observed when compared with healthy controls. The numbers of CD1a + and CD207+ DCs were not different between groups. In summary, high-risk HPV-related usual-type VIN lesions are characterized by an immunosuppressive state in the epidermis, showing a reduction of immature myeloid DCs (mDC) and CD8+ T cells. In the dermis, inflammatory activation is reflected by the influx of mature mDCs and pDCs, NK cells, and T cells, suggesting that the cellular immune response on viral HPV infection occurs in the dermis of VIN patients.

Reduced local immunity in HPV-related VIN: Expression of chemokines and involvement of immunocompetent cells (Article)

2008-08-01T00:00:00Z

Usual type VIN is a premalignant disorder caused by persistent HPV infection. High prevalence of VIN in immuno-suppressed women suggests that a good innate and adaptive immune response is important for defense against HPV. Here, we explored expression levels of chemokines and related these to the presence or absence of immuno-competent cells (dendritic and T-cells) in affected (HPV-positive VIN) and non-affected (HPV-negative) vulvar tissues from the same patients. Combining microarray data with quantitative real-time RT-PCR, it was observed that several important chemokines were differentially expressed between VIN and control samples (up-regulation of IL8, CXCL10, CCL20 and CCL22 and down-regulation of CXCL12, CCL21 and CCL14). Furthermore, an increased number of mature dendritic cells (CD208+) seemed to be bottled up in the dermis, and although a T-cell response (increased CD4+and CD8+cells) was observed in VIN, a much larger response is required to clear the infection. In summary, it seems that most mature dendritic cells do not receive the proper chemokine signal for migration and will stay in the dermis, not able to present viral antigen to naive T-cells in the lymph node. Consequently the adaptive immune response diminishes, resulting in a persistent HPV infection with increased risk for neoplasia.

Treatment of vulvar intraepithelial neoplasia with topical imiquimod (Article)

2008-04-03T00:00:00Z

Background: Alternatives to surgery are needed for the treatment of vulvar intraepithelial neoplasia. We investigated the effectiveness of imiquimod 5% cream, a topical immuneresponse modulator, for the treatment of this condition. Methods: Fifty-two patients with grade 2 or 3 vulvar intraepithelial neoplasia were randomly assigned to receive either imiquimod or placebo, applied twice weekly for 16 weeks. The primary outcome was a reduction of more than 25% in lesion size at 20 weeks. Secondary outcomes were histologic regression, clearance of human papillomavirus (HPV) from the lesion, changes in immune cells in the epidermis and dermis of the vulva, relief of symptoms, improvement of quality of life, and durability of response. Reduction in lesion size was classified as complete response (elimination), strong partial response (76 to 99% reduction), weak partial response (26 to 75% reduction), or no response (≤25% reduction). The follow-up period was 12 months. Results: Lesion size was reduced by more than 25% at 20 weeks in 21 of the 26 patients (81%) treated with imiquimod and in none of those treated with placebo (P<0.001). Histologic regression was significantly greater in the imiquimod group than in the placebo group (P<0.001). At baseline, 50 patients (96%) tested positive for HPV DNA. HPV cleared from the lesion in 15 patients in the imiquimod group (58%), as compared with 2 in the placebo group (8%) (P<0.001). The number of immune epidermal cells increased significantly and the number of immune dermal cells decreased significantly with imiquimod as compared with placebo. Imiquimod reduced pruritus and pain at 20 weeks (P = 0.008 and P = 0.004, respectively) and at 12 months (P = 0.04 and P = 0.02, respectively). The lesion progressed to invasion (to a depth of <1 mm) in 3 of 49 patients (6%) followed for 12 months (2 in the placebo group and 1 in the imiquimod group). Nine patients, all treated with imiquimod, had a complete response at 20 weeks and remained free from disease at 12 months. Conclusions: Imiquimod is effective in the treatment of vulvar intraepithelial neoplasia. (Current Controlled Trials number, ISRCTN11290871.) Copyright

In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma (Article)

2005-01-01T00:00:00Z

Although dendritic cells (DCs) play an important role in sensitization to inhaled allergens, their function in ongoing T helper (Th)2 cell-mediated eosinophilic airway inflammation underlying bronchial asthma is currently unknown. Here, we show in an ovalbumin (OVA)-driven murine asthma model that airway DCs acquire a mature phenotype and interact with CD4(+) T cells within sites of peribronchial and perivascular inflammation. To study whether DCs contributed to inflammation, we depleted DCs from the airways of CD11c-diphtheria toxin (DT) receptor transgenic mice during the OVA aerosol challenge. Airway administration of DT depleted CD11c(+) DCs and alveolar macrophages and abolished the characteristic features of asthma, including eosinophilic inflammation, goblet cell hyperplasia, and bronchial hyperreactivity. In the absence of CD11c(+) cells, endogenous or adoptively transferred CD4(+) Th2 cells did not produce interleukin (IL)-4, IL-5, and IL-13 in response to OVA aerosol. In CD11c-depleted mice, eosinophilic inflammation and Th2 cytokine secretion were restored by adoptive transfer of CD11c(+) DCs, but not alveolar macrophages. These findings identify lung DCs as key proinflammatory cells that are necessary and sufficient for Th2 cell stimulation during ongoing airway inflammation.

Allergic rhinitis is a local disease: the role of local IgE production, basophils and mast cells (Doctoral Thesis)

2002-11-20T00:00:00Z

The introduction to this thesis summarizes the literature which indicates that there is a discrepancy between sensitisation and allergic disease. Two aspects which might play a role in this discrepancy are the differences between production and funtion of local versus systemic lgE and the differences in mast cell and basophil function in the blood compared to in the tissues. Mast cells, basophils and IgE are key players in the allergic inflammation. The aim of the studies described in this thesis was to focus on these differences between local and systemic function of these key factors. The research questions addressed in this thesis are: Mast cells and basophils seem to play an important role in the pathogenesis of allergic rhinitis. Do the phenotypes of mast cells and basophilic cells changed by allergen provocation in the nasal mucosa of allergic rhinitis patients (Chapter 3)? The developmental relationship bet\veen mast cells and basophils has not yet been totally resolved. What is the relation bet\veen basophil progenitors, mast cell progenitors, basophils and mast cells in the circulation and in the nasal mucosa (Chapter 3)? Allergic mucosa inflammation is regulated by the local production and release of several Th2 cytokines. Which increase in cytokines and chemokines is correlated to inflammatory cells and symptomatology of the patient? What is the time line of the various cytokines and chemokines after allergen provocation (Chapter 4)? Is it possible to develop a method to detect specific lgE in tissues. Does production of specific IgE take place locally in the nasal mucosa (Chapter 5)? Where do basophils and mast-cell of allergic rhinitis patients acquire IgE (Chapter 5)? To adress these questions multiple blood samples and biopsies of the nasal mucosa of allergic patients were taken before, during and after allergen provocation. Cellular infiltrates in these biopsies were compared to those in biopsies of normal controls. Cell phenotypes, production and release of mediators and cytokines were studied using immunohistochemical techniques and in situ hybridisation.

Segmental bronchoprovocation in allergic rhinitis patients affects mast cell and basophil numbers in nasal and bronchial mucosa (Article)

2001-01-01T00:00:00Z

Mast cells and basophils are cells that play an important role in the initiation and control of allergic inflammation in asthma and rhinitis. This study was undertaken to determine the presence and dynamics of mast cells and basophils in the nasal and bronchial mucosa of allergic rhinitis patients after segmental bronchial provocation (SBP). Eight nonasthmatic, grass pollen-allergic rhinitis patients and eight healthy controls were included. Bronchial and nasal biopsies, as well as blood samples, were taken before (T(0)) and 24 h (T(24)) after SBP. Immunohistochemical staining was performed for mast cells (tryptase and chymase; phenotypes MC(T), MC(TC), MC(C)) and basophils (BB1). In the bronchial mucosa, the number of BB1(+) cells increased significantly (p < 0.05) in allergic rhinitis patients after SBP. In the nasal mucosa, the numbers of MC(C) and MC(TC) cells decreased significantly, whereas the numbers of [BB1(+)] cells increased significantly in allergic rhinitis patients after SBP (p < 0.05). In blood, the number of basophils decreased (p < 0.05) and the level of interleukin (IL)-5 increased (p < 0.05) in atopic patients after SBP. No significant changes could be observed in healthy controls. This study shows that SBP in nonasthmatic allergic rhinitis patients reduces numbers of mast cells in the nose as a result of enhanced degranulation. At the same time, there is evidence for an influx of basophils from the blood into the nasal and bronchial mucosae.

Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients (Article)

2000-01-01T00:00:00Z

Allergic diseases are characterized by allergic complaints in the shock organ and specific immunoglobulin (Ig)E in serum. Literature data indicate that the nasal mucosa itself could produce at least a large part of the specific IgE in allergic rhinitis patients. In order to investigate this hypothesis, nasal mucosal biopsies from the inferior turbinate were taken from symptomatic grass pollen allergic rhinitis patients, symptomatic house dust mite allergic rhinitis patients and nonallergic healthy controls, confirmed by radioallergosorbent test and skin-prick test. Immunohistochemical double-staining was performed for B-cells (CD19) with IgE, plasma cells (CD138) with IgE and plasma cells with biotinylated allergens. Significantly more IgE-positive B-cells and IgE-positive plasma cells were found in the nasal mucosa of allergic patients than in that of nonallergic controls. Double staining with biotinylated allergens and plasma cells showed allergen-positive plasma cells in the nasal mucosa of allergic patients and no allergen-positive plasma cells in the nasal mucosa of nonallergic patients. Blocking experiments using polyclonal antibodies directed against IgE showed a significant reduction in the number of allergen-positive cells in contrast to experiments using polyclonal antibodies directed against IgG, IgA or IgM. This study describes new evidence that specific immunoglobulin E is produced locally in the nasal mucosa in patients with seasonal allergic rhinitis and perennial allergic rhinitis, but not in nonallergic controls.

Segmental bronchial provocation induces nasal inflammation in allergic rhinitis patients (Article)

2000-01-01T00:00:00Z

Allergic rhinitis and asthma often coexist and share a genetic background. Pathophysiologic connections between the nose and lungs are still not entirely understood. This study was undertaken to compare allergic inflammation and clinical findings in the upper and lower airways after segmental bronchial provocation (SBP) in nonasthmatic allergic rhinitis patients. Eight nonasthmatic, grass pollen-sensitive patients with allergic rhinitis and eight healthy controls were included. Bronchial biopsies and blood samples were taken before (T(0)) and 24 h (T(24)) after SBP. Nasal biopsies were obtained at T(0), 1 h after SBP (T(1)), and T(24). Immunohistochemical staining was performed for eosinophils (BMK13), interleukin (IL)-5, and eotaxin. The number of eosinophils increased in the challenged and unchallenged bronchial mucosa (p < 0.05) and in the blood (p = 0.03) of atopic subjects at T(24). We detected an increase of BMK13-positive and eotaxin-positive cells in the nasal lamina propria and enhanced expression of IL-5 in the nasal epithelium of atopic subjects only at T(24) (p < 0.05). SBP induced nasal and bronchial symptoms as well as reductions in pulmonary and nasal function in the allergic group. No significant changes could be observed in healthy controls. The study shows that SBP in nonasthmatic allergic rhinitis patients results in peripheral blood eosinophilia, and that SBP can induce allergic inflammation in the nose.

Type 1-like immune response is found in children with Respiratory Syncytial Virus infection regardless of clinical severity. (Article)

2000-01-01T00:00:00Z

The immunological response of infants younger than six months to infection with respiratory syncytial virus (RSV) was studied in relation to clinical severity. IL-6 and IL-8 were found more frequently and at higher levels in the plasma samples of more severely ill patients and no significant differences were found in the levels of cytokines differentiating between Type 1 and Type 2 responses. Cellular infiltrates in nasopharyngeal washings consisted mainly of polymorphonuclear granulocytes and monocytes. Eosinophils, IgE positive cells and tryptase positive cells were found sporadically. Analyses of RSV stimulated T cell cultures established from peripheral blood mononuclear cells, for intracellular and secreted cytokines showed that, irrespective of clinical severity, the responses were dominated by the production of IFN-γ, and that only low levels of IL-4 and IL-10 were detectable. Collectively these data do not indicate an association between clinical severity and a Type 2-like T cell response.

Differences in nasal cellular infiltrates between allergic children and age-matched controls (Article)

1999-01-01T00:00:00Z

Little is known about the cellular infiltrates in the nasal mucosa of children. This study was set up to compare the nasal cellular infiltrates in biopsy specimens from allergic children and controls. Atopic children were distinguished from controls on the basis of symptoms of allergic rhinitis and/or asthma, total serum immunoglobulin (Ig)E, family history and specific serum IgE to food and aeroallergens. Fifteen allergic patients (median age 4.3 yrs) and 15 age-matched nonallergic control subjects were evaluated. The number of cells positive for CD1a, CD4, CD8, CD19, CD68, chymase, tryptase, IgE and major basic protein was determined in the mucosa of the inferior turbinate. A significantly higher number of IgE-positive cells and mast cells was found in the epithelia of the allergic group. In the lamina propria, higher numbers of IgE-positive cells and eosinophils were found. Langerhans' cells positive for IgE were only seen in allergic children with specific serum IgE against aeroallergens. These children also had a higher number of IgE-positive mast cells compared to controls and atopic children without specific serum IgE. These results show that the nasal cellular infiltrates of allergic children differ from nonallergic control subjects. Prior to the detection of specific serum immunoglobulin E, cellular changes can be found in the nasal mucosa of atopic children.