Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production: inhibition by a non-anaphylactogenic anti-IgE antibody.

Abstract

SummaryElevated levels of immunoglobulin (Ig) E are associated with bronchial asthma, a disease characterized by eosinophilic inflammation of the airways. Activation of antigen-specific T helper (Th) 2 cells in the lung with the subsequent release ofinterleukin (IL) 4 and IL-5 is believed to play an important role in the pathogenesis of this disease. In this study, we have used a nonanaphylactogenic anti-mouse-IgE antibody to investigate the relationship between IgE, airway eosinophil infiltration, and the production ofTh2 cytokines. Immunization of mice with house dust mite antigen increased serum levels of IgE and IgG. Antigen challenge of immunized but not control mice induced an infiltration ofeosinophils in the bronchoalveolar lavage associated with the production of IL-4 and IL-5 from lung purified Thyl.2 + cells activated through the CD3-T cell receptor complex. Administration of the anti-IgE monoclonal antibody (mAb) 6 h before antigen challenge neutralized serum IgE but not IgG and inhibited the recruitment of eosinophils into the lungs and the production of IL-4 and IL-5 but not interferon ~/. Studies performed using an anti-CD23 mAb, CD23 deficient and mast cell deficient mice suggest that anti-IgE mAb suppresses eosinophil infiltration and Th2 cytokine production by inhibiting IgE-CD23-facilitated antigen presentation to T cells. Our results demonstrate that IgE-dependent mechanisms are important in the induction ofa Th2 immune response and the subsequent infiltration ofeosinophils into the airways. Neutralization oflgE by, for example, non-anaphylactogenic anti-IgE mAbs may provide a novel therapeutic approach to the treatment of allergic airway disease.

House dust mite-specific IgE antibodies in induced sputum are associated with sputum eosinophilia in mite-sensitive asthmatics

“…18 In the mouse model, administration of the anti-IgE monoclonal antibody before allergen challenge inhibited the recruitment of eosinophils into the lungs and the production of IL-4 and IL-5. 19 These reports are consistent with our in vivo study results demonstrating significant association between sputum eosinophilia and allergen-specific IgE antibodies in induced sputum from atopic asthmatic patients. In this study, sputum sampling was done during the peak season of natural house dust mite exposure, 10 thus our patients might have been under chronic natural allergen challenge.…”

Interleukin-31 promotes helper T cell type-2 inflammation in children with allergic rhinitis

“…The eosinophil infiltration, release of ECP, and IgE production were important features of AR (16). Thus, we detected eosinophil counts and examined IgE and ECP expression and their relation with IL-31.…”

Complement C3a-Induced IL-17 Plays a Critical Role in an IgE-Mediated Late-Phase Asthmatic Response and Airway Hyperresponsiveness via Neutrophilic Inflammation in Mice

“…Meanwhile, several clinical and experimental investigations have suggested that Agspecific memory T cells, especially CD4 + T cells, play an integral role in orchestrating chronic asthmatic responses such as the late response, AHR, and airway inflammation through the secretion of a variety of Th2-type cytokines including IL-4, IL-5, and IL-13 (2,(5)(6)(7)(8). Additionally, IgE has the capacity to induce the production of Th2-type cytokines and the development of airway inflammation and AHR in mice (9)(10)(11), indicating the importance of IgE in chronic asthmatic responses. More interestingly, in clinical studies, the severity of symptoms in some poorly controlled asthmatic patients was improved by treatment with a humanized anti-IgE Ab (12)(13)(14).…”