The IgE response in allergic asthmatic patients : the SCID mouse model

Abstract

Summary Asthma is defined by three main critera : reversible airway obstruction, airway inflammation and increased airway responsiveness in response to non specific stimuli like histamine and carbachol, associated with an enhancement of the IgE production in allergic asthma. To evaluate the exact role linked to these different components of asthma, several experimental models have been proposed but results obtained are for a large part depending on the species tested and/or of the sensitization protocol used. It is the reason why we recently studied the effects of the reconstitution of SCID mice with peripheral blood mononuclear cells (PBMC) obtained from asthmatic patients sensitive to Dermatophagoides pteronyssinus. Experiments showed that humanized SCID mice have the capacity to develop a specific IgE response, especially after immunization with the related allergen. Moreover after repeated allergen exposure by inhalation, reconstituted SCID mice demonstrated an inflammatory reaction prodominant around pulmonary vessels and in small bronchi under the epithelial layer. Analysis of cell populations demonstrated the presence of CD45 RO+ Tcells, HLA-DR+ cells and some eosinophils probably of murine origin. In addition SCID mice reconstituted with PBMC of allergic asthmatics exhibited an increased bronchial hyperresponsiveness (BHR) to carbachol. So the SCID mouse model allows to identify the 3 main characteristics of allergic asthma: human IgE production, human cell infiltration and BHR, even if the characteristics of the inflammatory response are not exactly similar to that found in bronchial asthma.