The factors that contribute to allergic asthma are unclear but the resulting condition is considered a consequence of a type-2 T helper (TH2) cell response. In a model of pulmonary allergic inflammation, mice that lacked gammadelta T cells had decreases in specific immunoglobulin E (IgE) and IgG1 and pulmonary interleukin-5 (IL-5) release as well as in eosinophil and T cell infiltration compared with wild-type mice. These responses were restored by administration of IL-4 to gammadelta T cell-deficient mice during the primary immunization. Thus, gammadelta T cells are essential for inducing IL-4-dependent IgE and IgG1 responses and for TH2-mediated airway inflammation to peptidic antigens.

This report examines the effect of recombinant murine (rm)IL-10 on antigen-induced cellular recruitment into the airways of sensitized Balb/c mice. The intranasal instillation of 10 pug ovalbumin induced an early (6-24 h) increase in the number of neutrophils, and a late rise (24-96 h) in that of eosinophils in the bronchoalveolar lavage (BAL) fluid and bronchial tissue. A single intranasal instillation of 0.01-0

A murine model for antigen-induced bronchial hyperreactivity (BHR) and airway eosinophilia, two hallmarks of asthma, was developed using ovalbuminimmunized mice, which produce large amounts of IgE (named BP2, "Bons Producteurs 2," for High Line of Selection 2). A single intranasal ovalbumin challenge failed to modify the bronchial responses, despite the intense eosinophil recruitment into the bronchoalveolar lavage fluid and airways. When mice were challenged twice a day for 2 days or once a day for 10 days, BHR in response to i.v. 5-hydroxytryptamine or to inhaled methacholine was induced in BP2 mice but not in BALB/c mice. Histological examination showed that eosinophils reached the respiratory epithelium after multiple ovalbumin challenges in BP2 mice but remained in the bronchial submucosa in BALB/c mice. Total IgE titers in serum were augmented significantly with immunization in both strains, but much more so in BP2 mice. Interleukin 5 (IL-5) titers in serum and bronchoalveolar lavage fluid of BP2 mice were augmented by the antigenic provocation, and a specific anti-IL-5 neutralizing antibody suppressed altogether airway eosinophilia and BHR, indicating a participation of IL-5 in its development. Our results indicate that the recruitment of eosinophils to the airways alone does not induce BHR in mice and that the selective effect on BP2 mice is related to their increased IgE titers associated with antigen-driven eosinophil migration to the epithelium, following formation and secretion of IL-5.Bronchial hyperreactivity (BHR) Evaluation of Bronchoconstriction. In a first procedure, mice were prepared as described (5), using the computerized pulmonary analyzer (Mumed PR800 system, UK) adapted to mice. To evaluate the effect of antigenic challenge on airway responsiveness, 5-hydroxytryptamine (5-HT; Sigma) was injected into the cannulated jugular vein at 10, 20, 40, 80, 160, and 320 jig/kg in a volume of 100 ,ul during 10 sec at 5-min intervals. The results were expressed as PD30, PD60, and PD90 (the amount of 5-HT needed to augment the bronchial resistance by 30%, 60%, and 90%). In a second procedure, unrestrained conscious mice were placed in a whole body plethysmographic chamber (Buxco Electronics, Sharon, CT) to analyze the respiratory waveforms. After a few minutes for stabilization, an aerosol of methacholine (3 x 10-2 M in the aerosolator; Aldrich) was delivered during 20 and 60 sec, at a 10-min interval. The airway resistance was expressed as Penh = [Te (expiratory time)/40% of Tr (relaxation time) -1] x Pef (peak expiratory flow)/Pif (peak inspiratory flow) x 0.67, according to the recommendations of the manufacturer. To calculate the APenh (difference between the basal and maximal value), the average of five maximal values was used.