Studies will define the ability of eosinophils to serve as antigen- presenting cells that may contribute to propagating lymphocyte- dependent, IgE-mediated responses to inhaled antigens in the respiratory tract. Eosinophils are prominent cellular components of allergic airway responses, although eosinophils are usually considered to have their principal roles in allergic inflammation by exerting """"""""end-stage"""""""" effector cell activities (e.g., degranulation and mediator release). While many cells function as antigen-presenting cells, eosinophils have distinct capabilities within the airway. First, eosinophils present within the airways and recovered from the sputum of asthmatics and from bronchoalveolar lavage fluid following antigen challenge have already been induced in vivo to express the requisite Class II MHC proteins. Second, unlike B cells and dendritic cells that are capable of presenting soluble antigens, eosinophils, like macrophages, degrade particulate antigens. Although alveolar macrophages are poor antigen-presenting cells, eosinophils would be able to present peptides derived from normally particulate, inhaled allergens. Third, antibodies, by Fc receptor-mediated mechanisms, dramatically enhance presentation by antigen-presenting cells. Eosinophils with their IgE, IgA and IgG receptors are well-suited to present allergens recognized by IgE, IgA and IgG antibodies to these allergens present in the respiratory tract. Fourth, eosinophil traffic from the airway lumen to tissues would provide a mechanism for antigens inhaled into the airways to be both processed and transported into tissues for presentation to lymphocytes. The hypotheses are that eosinophils are effective at presenting particulate antigens to lymphocytes, that eosinophil antigen processing occurs in vivo within the airways, and that eosinophil high affinity IgE receptors function to enhance eosinophil antigen presentation of allergens. The studies aim to define the capacity of human eosinophils in vitro and murine eosinophils in vivo to function as antigen-presenting cells and to define the role of eosinophil IgE receptors in facilitating antigen presentation by eosinophils. These studies of eosinophils active in asthma include a focus on the roles of IgE and IgE receptors on eosinophils in propagating the chronic airway inflammation of asthma and will utilize transgenic murine eosinophils expressing humanized FcepsilonRI. Roles for eosinophils as antigen-presenting cells in sustaining allergic responses to inhaled particulate allergens would provide novel insights into the characteristically chronic nature of allergic diseases.
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