BACKGROUND: We have shown previously that the late airways response (LAR) can be transferred by ovalbumin-primed CD4(+) T lymphocytes in Brown Norway rats. This response is associated with an increase of eosinophils and high expression of TH2 cytokines (IL-4 and IL-5) in bronchoalveolar lavage (BAL) fluid. OBJECTIVE: In this study we hypothesized that the inhibition of IL-4 or IL-5 production in the CD4(+) cells transferred to a naive animal could decrease the LAR and prevent airway eosinophilia in response to antigen challenge. METHODS: CD4(+) cells, purified from the cervical lymph nodes of ovalbumin-sensitized rats, were maintained in culture for 6 hours with medium alone or with 10 microgram/mL IL-4 antisense (AS), IL-5 AS, or control AS oligodeoxynucleotide. Then the cells were administrated intraperitoneally to naive rats, which were challenged 2 days later by a 5% ovalbumin aerosol. The lung resistance was measured for 8 hours, and then BAL was performed. Cytospin preparations from BAL cells were assessed for the presence of eosinophils by immunocytochemistry for major basic protein and for IL-4, IL-5, and IFN-gamma expression. RESULTS: In rats injected with IL-4 AS-treated T cells, LAR, eosinophils, and IL-4 and IL-5 expression were significantly decreased compared with the other groups. Only IL-5 expression in BAL fluid was slightly decreased consequent to the transfer of IL-5 AS-treated T cells. CONCLUSION: This study demonstrates that, in the CD4(+) T cell-driven LAR, the early production of IL-4, but not IL-5, by the transferred CD4(+) cells is essential for the development of the LAR.
The age-related peculiarities of indices of the total and specific immunity systems were comparatively studied in children with atopic bronchial asthma (ABA) at critical age intervals. The group of children aged 2 to 5 was shown to have a higher absolute quantity of CD3+, CD4+ and CD8+ lymphocytes, a relatively lower content of CD8+ and CD16+ lymphocytes, disimmunoglobulinemia, a higher level of total IgE (by 36.5 times), and an impaired functional activity of cells in the nonspecific resistance system. Higher levels of specific IgE-antibodies to pollen allergens were detected in 84.4% of cases in peripheral blood of ABA children; the content of the above antibodies (to mixed weed allergens, hemp, fescue, boon, bent, ryegrass, and sun-flower) were higher (p
BACKGROUND: Macrophages are involved in asthma, but their pulmonary turnover is unknown. We compared the ability of bronchoalveolar lavage (BAL) and bronchial macrophages to proliferate in normal subjects and patients with asthma. METHODS: BAL cells from eight patients with asthma and eight normal volunteers were separated with a discontinuous Percoll gradient (Pharmacia Fine Chemicals, Uppsala, Sweden). In a first experiment, nuclei of each alveolar macrophage (AM) fraction, stained with propidium iodide, were analyzed for DNA content with a flow cytometer, and the proportions of cells in the G0/G1, S, and G2 + M phases were determined. In a second experiment, expression of Ki-67-related antigen was sought on AMs by immunocytochemistry. Macrophages from 10 patients with asthma and 10 normal volunteers were studied in biopsy specimens by means of immunohistochemistry with a panmacrophage monoclonal antibody (HAM-56) and a monoclonal antibody against proliferating cell nuclear antigen. RESULTS: The proportions of BAL AMs in the different phases of the cell cycle were similar in normal subjects and patients with asthma for all fractions, and the percentage of cells in S and G2 +/- M phases ranged from 7.3% to 11.3%. Under 1% of BAL AMs expressed Ki-67-related antigen. None of the macrophages present in the biopsy specimens expressed proliferating cell nuclear antigen. CONCLUSIONS: This study does not indicate that an important source of airway macrophages is local proliferation.
BACKGROUND: In general, the non-pyroglyphid mites Lepidoglyphus destructor and Blomia tropicalis show a different geographical distribution. Allergic sensitization to both species have been demonstrated in several investigations. However, whether this reflects cross-reactivity or dual sensitization is so far not known. OBJECTIVE: The aim of the study was to investigate the allergenicity and allergenic crossreactivity of L. destructor and B. tropicalis using sera from Sweden and Brazil. METHODS: Allergens in extracts of L. destructor and B. tropicalis were identified with SDS-PAGE and immunoblotting and the crossreactivity was studied by an immunoblot inhibition method. In addition to mite extracts, a recombinant major allergen of L. destructor, Lep d 2, was used. RESULTS: The extract prepared from L. destructor contained 21 IgE-binding components when using the Swedish or the Brazilian sera. A 15 kDa allergen was recognized by 85% of the Swedish sera and 78% of the Brazilian. The B. tropicalis extract exposed 23 IgE-binding components when the Brazilian sera were used and 19 when the Swedish sera were used. A total of 83% of the Brazilian sera and 80% of the Swedish sera identified a 14.5 kDa allergen. The IgE response of the Swedish serum pool to 10 B. tropicalis allergens was inhibited by L. destructor extract. Likewise, the response of the Brazilian serum pool to four different L. destructor allergens was inhibited by B. tropicalis extract. The recombinant Lep d 2 allergen inhibited 33% of the IgE binding of the Swedish serum pool to the 14.5 kDa allergen in the B. tropicalis extract. CONCLUSION: Crossreactivity with several proteins from L. destructor and B. tropicalis was demonstrated. The results suggest that a B. tropicalis 14.5 kDa allergen is antigenically crossreactive with recombinant L. destructor allergen Lep d 2.
Allergists around the world have different practice styles when administering subcutaneous aeroallergen immunotherapy (IT) in peak pollen seasons, especially when changing doses or frequency of IT. The Immunotherapy practice parameters do not specifically address this issue.
Given the paucity of good data about adjustment of allergen immunotherapy during the pollen seasons, we examined whether a significant difference is present in the way allergists administer immunotherapy during allergy seasons.
To quantify the practice styles of allergists who are members of the American Academy of Allergy, Asthma and Immunology (AAAAI), a self-reported electronic survey was disseminated in September 2010 with the help of the AAAAI Needs Assessment Committee. The responses were tallied and analyzed according to demographic information.
A total of 1,201 allergists in the AAAAI responded to the survey. Most responders practice in an urban or suburban nonacademic practice in the United States and have been in practice for more than 10 years. The size of their practice was variable. Those in practice for more than 10 years were more likely to adjust the dose and frequency of immunotherapy in pollen seasons.
This survey highlights the differences in the practice styles of AAAAI member allergists, and these differences may be associated with their demographic characteristics. Given the wide variability in how allergists adjust dose and frequency of immunotherapy during pollen seasons, establishing guidelines regarding this routine dilemma might help standardize the delivery of treatment to patients.
BACKGROUND: We have previously reported an association between low IgA and allergic manifestations in early childhood (0-2 years) and have now followed our cohort for an additional 2 years. OBJECTIVE: To evaluate in a longitudinal community-based cohort study the association between maturation of Ig production and allergic manifestations in the first 4 years of life. METHODS: A cohort of 161 randomly selected children was followed from birth to the age of 42-48 months and evaluated at 18-23 months (EV1; n = 179) and again at the age of 42-48 months (EV2; n = 161). Diagnoses were made with the help of a clinical questionnaire, physical examination and skin prick tests (SPTs) to 10 common allergens. Serum immunoglobulins were measured at EV1 and EV2, and salivary IgA (sal-IgA) at EV2. RESULTS: Serum IgA, IgE, IgG1, IgG2 and IgG4 increased from 2 to 4 years of age (P
Brown Norway rats are widely used as a model of asthma, whereas Sprague Dawley rats do not develop allergic reactions under the same conditions. Given the importance of alveolar macrophages (AM) in down-regulating cellular immune responses in the lung, we postulated that the different susceptibilities in the development of airway allergic reactions in these rat strains may be related to functional differences in their AM. We investigated the production of important mediators in asthma, namely tumour necrosis factor (TNF), interleukin-10 (IL-10), IL-12, IL-13, nitric oxide (NO) and macrophage inflammatory protein-1alpha (MIP-1alpha), by AM of unsensitized Sprague Dawley and Brown Norway rats. AM were purified by adherence and stimulated with OX8 (anti-CD8 antibody) or LPS. OX8 stimulation significantly increased the release of TNF, IL-10 and NO in both strains of rats, whereas MIP-1alpha and IL-12 release were increased in Brown Norway rats only. Interestingly, stimulated AM from Sprague Dawley rats released significantly more TNF and less IL-10, IL-12, IL-13, MIP-1alpha and NO compared with AM from Brown Norway rats. These differences were also observed at the mRNA level, except for TNF. Thus, AM from Brown Norway and Sprague Dawley rats are functionally different. Furthermore, LPS- and OX8-stimulated AM from Brown Norway rats produce more Th2 type cytokines (IL-10 and IL-13) than AM from Sprague Dawley rats, suggesting that these cells may play an important role in creating a cytokine milieu that may favour the development of allergic reactions.
We measured airway responsiveness to methacholine (MCh) of highly inbred rats before and after six inhalational challenges with antigen. Ten Brown-Norway rats (130-216 g) that were actively sensitized to ovalbumin (OA) received six challenges with OA at 5-day intervals beginning 19 days after sensitization. An aerosol of OA (5% wt/vol) was inhaled for 1, 2, 5, and 10 min or until pulmonary resistance (RL) increased by at least 50%. Challenges with aerosolized MCh were performed immediately before and 14 days after sensitization, 2 days after the 3rd OA exposure, and 2, 7, 12, and 17 days after the 6th OA challenge. Four unsensitized rats underwent inhalational challenges with MCh over an equivalent time period. Responsiveness to MCh was calculated as the concentration of MCh required to increase RL to 200% of the control value (EC200RL). Seven out of 10 rats in the experimental group reacted to the first OA challenge with an immediate increase in RL of greater than 50% of control (range 70-550%). Three animals were unreactive to OA. Base-line EC200RL for all rats undergoing sensitization was 2.13 mg/ml (geometric mean), and it did not change significantly after sensitization (2.05 mg/ml). However, EC200RL of the rats that reacted to OA (n = 7) decreased significantly after 3 (1.11 mg/ml; P less than 0.005) and 6 OA exposures (0.96 mg/ml; P less than 0.005). The increase in responsiveness to inhaled MCh was present 17 days after the last OA exposure (EC200RL = 1.40 mg/ml; P less than 0.05). EC200RL of neither the unreactive sensitized rats (n = 3) nor the control rats (n = 4) changed after OA challenges.(ABSTRACT TRUNCATED AT 250 WORDS)