Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouse

Renz, Harald; Smith, Hunter; Henson, Jan E.; Ray, Bradley S.; Irvin, Charles G.; Gelfand, Erwin W.

doi:10.1016/0091-6749(92)90296-e

Cited by 251 publications

(212 citation statements)

References 41 publications

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“…Experimental models of respiratory Ag challenge have identified two major classes of Ag implicated in allergic lung disease. The first class, in this study termed type I, is exemplified by chicken egg OVA which, aside from airway hyperresponsiveness (1), is incapable of inducing a broad spectrum of lung allergic changes which additionally include goblet cell metaplasia, mucus oversecretion, airway eosinophilia, and peribronchovascular inflammation, if given strictly by inhalation. However, OVA is capable of inducing all of these allergic changes if given remote from the lung in a series of priming doses, typically with aluminum-based adjuvants before intrapulmonary challenge (2)(3)(4)(5)(6)(7)(8)(9)(10)(11).…”

Section: Efining the Immunopathologic Basis Of Allergic Inflam-mentioning

confidence: 99%

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

Kheradmand

Kiss

et al. 2002

The Journal of Immunology

287

292

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The respiratory allergens that induce experimental Th cell type 2-dependent allergic lung inflammation may be grouped into two functional classes. One class of allergens, in this study termed type I, requires priming with adjuvants remote from the lung to overcome airway tolerogenic mechanisms that ordinarily preclude allergic responses to inhaled Ags. In contrast, the other, or type II, allergen class requires neither remote priming nor additional adjuvants to overcome airway tolerance and elicit robust allergic lung disease. In this study, we show in an experimental model that diverse type II allergens share in common proteolytic activity that is both necessary and sufficient for overcoming airway tolerance and induction of pulmonary allergic disease. Inactivated protease and protease-free Ag fragments showed no allergenic potency, demonstrating that only active protease acting on endogenous substrates was essential. Furthermore, induction of airway tolerance could be aborted and allergic lung disease established by simply adding purified protease to a type I allergen. Thus, exogenous proteases are common to type II allergens and may be generally required to overcome the innate resistance of the airway to Th cell type 2 activation and allergic inflammation, raising concern for their potential contribution to diseases such as asthma.

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Section: Efining the Immunopathologic Basis Of Allergic Inflam-mentioning

confidence: 99%

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

Kheradmand

Kiss

et al. 2002

The Journal of Immunology

287

292

View full text Add to dashboard Cite

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“…17 IgE or IgG 1 were captured from serum (diluted 2-to 320,000-fold) using Immulon 2 microtiter plates (Dynatech Laboratories, Chantilly, VA) coated with antimouse IgE (R35-72) or anti-mouse IgG 1 (A85-3) (obtained from BD PharMingen, San Diego, CA) at 2 g/ml in 0.1 mol/L carbonate, pH 9.5. Detection was with an OVAdigoxigenin conjugate followed by horseradish peroxidase-conjugated anti-digoxigenin, essentially as described.…”

Section: Ova-specific Serum Ige and Igg 1 Levelsmentioning

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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“…In the model used, BALB͞c mice were sensitized (in the absence of adjuvant) exclusively via the airways, mimicking a ''natural'' mode of allergic sensitization to aeroallergens. Airway sensitization in this way induces allergen-specific IgE (13) and T cell activation (14), which is associated with immediate cutaneous hypersensitivity (15) and increased airway responsiveness (16). The development of airway hyperreactivity (AHR) in this model is associated with, or dependent on, three distinct events: allergen challenge of the airways, IL-5-mediated eosinophil airway infiltration, and production of allergen-specific IgE.…”

mentioning

confidence: 99%

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

Hamelmann

Vella

Oshiba

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

126

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B cells play an important role in the allergic response by producing allergen-specific Igs as well as by serving as antigen-presenting cells. We studied the involvement of B cells in the development of responses in a murine model of allergic airway sensitization. Normal and B celldeficient ( Mt ؊͞؊ ) B10.BR mice were sensitized via the airways to ovalbumin; Ig production, cytokine elaboration from local lymph node cells, development of airway hyperresponsiveness, and histological changes in the airways were evaluated. Both strains of mice had increased production of T helper 2-like cytokines and developed an accumulation of eosinophils in the bronchial tissue after airway sensitization. However, only wild-type mice produced allergen-specific antibodies and exhibited altered airway function. B cell-deficient mice reconstituted with anti-ovalbumin IgE during the course of sensitization developed increases in airway responsiveness. These results indicated that neither B cells nor IgE were necessary for the induction of a T helper 2-type cytokine response or eosinophil infiltration of the airways after allergic sensitization but that IgE was required as a second signal for the development of airway hyperresponsiveness in this model of airway sensitization.

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Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouse

Cited by 251 publications

References 41 publications

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

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

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

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