Allergic airway sensitization induces T cell activation but not airway hyperresponsiveness in B cell-deficient mice

Hamelmann, Eckard; Vella, Anthony T.; Oshiba, Akihiro; Kappler, John W.; Marrack, Philippa; Gelfand, Erwin W.

doi:10.1073/pnas.94.4.1350

Cited by 126 publications

(114 citation statements)

References 41 publications

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“…mMt ±/± mice receiving anti-TNP IgE during 10-day OA nebulization had ES 50 levels similar to those of OA-sensitized, untreated mMt ±/± mice. mice (38). This demonstrates that B cells and/or IgE itself is not essential for allergen-induced T-cell activation and con®rms reports showing B-cell-independent T-cell priming (39), T-cell memory (40,41), and T-cell tolerance (42,43).…”

supporting

confidence: 84%

Role of IgE in the development of allergic airway inflammation and airway hyperresponsiveness – a murine model

Hamelmann

Tadeda

Oshiba

et al. 1999

Allergy

183

135

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supporting

confidence: 84%

Role of IgE in the development of allergic airway inflammation and airway hyperresponsiveness – a murine model

Hamelmann

Tadeda

Oshiba

et al. 1999

Allergy

183

135

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“…Experiments in animals suggest that the early asthmatic response is dependent on antigen-specific IgE (Lambert et al, 1998). Some investigators have suggested that AHR may be dependent on IL-4, which plays a major role in the induction of an IgE response, or on IgE itself (Brusselle et al, 1995;Corry et al, 1996;Hamelmann et al, 1997b). Several reports also indicate that IL-5, which regulates accumulation of eosinophils, plays an important role in AHR and the pathophysiology of changes in the respiratory epithelium (Foster et al, 1996;Hogan et al, 1997a;1998a;Kung et al, 1995;Nakajima et al, 1992).…”

mentioning

confidence: 99%

Dissociation of Inflammatory and Epithelial Responses in a Murine Model of Chronic Asthma

Foster

Yang

Matthei

et al. 2000

Laboratory Investigation

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SUMMARY:To study pathogenetic mechanisms in chronic asthma, we employed a novel experimental model that replicates characteristic features of the human disease. Chronic inflammation and epithelial changes, specifically localized to the airways, were induced by repeated exposure of systemically sensitized BALB/c mice to low mass concentrations of aerosolized ovalbumin for 6 weeks. The contribution of Th2 cytokine-driven inflammation to the development of airway lesions and hyperreactivity was assessed in cytokine-deficient mice. In interleukin-5-deficient animals, intraepithelial eosinophils and chronic inflammatory cells in the lamina propria of the airways were markedly decreased; however, these animals developed epithelial hypertrophy and subepithelial fibrosis comparable with that observed in sensitized wild type mice. Airway hyperreactivity to inhaled methacholine did not develop in interleukin-5-deficient mice. In contrast, interleukin-4-deficient mice exhibited no decrease in airway inflammation, but had significantly greater epithelial hypertrophy and subepithelial fibrosis, as well as exaggerated hyperreactivity to methacholine. We conclude that interleukin-5, but not interleukin-4, plays a central role in the development of chronic inflammation of the airways and the induction of airway hyperreactivity. Furthermore, chronic epithelial and fibrotic changes occur independently of interleukin-5 and are not required for the development of airway hyperreactivity. The dissociation between airway wall remodeling and airway hyperreactivity has important implications for therapeutic approaches to chronic asthma. (Lab Invest 2000, 80:655-662).

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“…[5][6][7][8][9][10] However, these responses have typically been assessed in isolation from each other. We have recently demonstrated that C57BL/6J mice undergo a biphasic response to aerosolized ovalbumin (OVA) exposure.…”

mentioning

confidence: 99%

Chronic Inhaled Ovalbumin Exposure Induces Antigen-Dependent but Not Antigen-Specific Inhalational Tolerance in a Murine Model of Allergic Airway Disease

Schramm

Puddington

et al. 2004

The American Journal of Pathology

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Sensitized mice acutely challenged with inhaled ovalbumin (OVA) develop allergic airway inflammation, characterized by OVA-specific IgE production, airway eosinophilia, increased pulmonary B and T lymphocytes, and airway hyperreactivity. In this study, a chronic exposure model was developed and two distinct patterns of response were observed. Discontinuous inhalational exposure to OVA (6 weeks) produced airway inflammation and hyperreactivity that were similar to acute (10 days) responses. Continuous inhalational exposure to OVA (6 or 11 weeks) resulted in attenuation of airway eosinophilia and hyperresponsiveness without reduction of OVA-specific IgE and IgG 1 levels. The inhibition of airway inflammation was dependent on continuous exposure to antigen, because continuously exposed mice with attenuated inflammatory responses redeveloped allergic airway disease if the OVA aerosols were interrupted and then restarted (11-week-discontinuous). Inhalational tolerance induced by continuous OVA exposure demonstrated bystander suppression of cockroach allergen-mediated airway eosinophilia. These findings may be attributed to changes in production of the anti-inflammatory cytokine interleukin-10 during continuous OVA aerosol exposure. The symptomatic and asymptomatic allergic responses in human asthmatics could be explained by similar variable or discontinuous exposures to aeroantigens. Throughout the past 40 years, the prevalence of allergic disease, including atopic dermatitis, hay fever, and asthma, has risen dramatically in the developed world. This disturbing trend is documented best for asthma. 1,2 A wealth of clinical and experimental data suggests that allergic asthma is due to an aberrant lung immune response mediated through T-helper type 2 cells (Th2 cells) and associated cytokine-signaling pathways. The normal lung is able to distinguish between airborne antigens associated with infectious agents, to which an immunological response is generated, and harmless inhaled antigens, which are usually ignored. In the asthmatic lung, some of these normally harmless antigens activate specific Th2 cells and elicit an inflammatory response characterized by Th2 cytokine production, eosinophilic airway inflammation, airway hyperresponsiveness, and bronchoconstriction. These pulmonary responses may be accompanied by systemic allergic sensitization, manifested by elevated titers of antigen-specific IgE. The mechanisms that control CD4 ϩ T lymphocyte polarization to allergenic Th2 phenotypes are incompletely understood but seem to involve genetic predispositions, local factors such as pre-existing cytokine concentrations and inflammation, and antigenic factors (ie, potency, dose, and duration of exposure).Several investigators have used mouse models to investigate the mechanisms of inhalational tolerance to antigens 3,4 or of allergic airway sensitization. [5][6][7][8][9][10] However, these responses have typically been assessed in isolation from each other. We have recently demonstrated that C57BL/6J mice undergo a biphasic...

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Allergic airway sensitization induces T cell activation but not airway hyperresponsiveness in B cell-deficient mice

Cited by 126 publications

References 41 publications

Role of IgE in the development of allergic airway inflammation and airway hyperresponsiveness – a murine model

Role of IgE in the development of allergic airway inflammation and airway hyperresponsiveness – a murine model

Dissociation of Inflammatory and Epithelial Responses in a Murine Model of Chronic Asthma

Chronic Inhaled Ovalbumin Exposure Induces Antigen-Dependent but Not Antigen-Specific Inhalational Tolerance in a Murine Model of Allergic Airway Disease

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