Studies will investigate the ability of eosinophils to serve as antigen-presenting cells that contribute to propagating lymphocyte-dependent, IgE-mediated response to inhaled antigens in the respiratory tract. Eosinophils are prominent cellular components of allergic airway responses. While many cells function as antigen-presenting cells, eosinophils have distinct capabilities within the airway. First, eosinophils are present in the airway lumina of asthmatics; and these eosinophils in vivo express requisite class II MHC proteins and critical lymphocyte costimulatory proteins. Second, eosinophils contain preformed stores of cytokines that may be rapidly mobilized for extra cellular release to modulate lymphocyte-dependent responses. Third, unlike B cells and dendritic cells that are capable of presenting soluble protein antigens, eosinophils, like macrophages, are especially able to degrade particulate antigens. Alveolar macrophages are poor antigen-presenting cells. In contrast, eosinophils could present peptides derived from particulate inhaled allergens. Fourth, antibodies of several classes, by Fc receptor-mediated mechanisms, can dramatically enhance antigen uptake and presentation by antigen-presenting cells. Eosinophils with their IgE, IgA, and IgG antibodies receptors are well suited to internalize and present allergens recognized by allergen-specific IgE, IgA, and IgG antibodies present in the respiratory tract. Fifth, eosinophil trafficking from the airway lumen into lymphocytes provides a mechanism for antigens inhaled into the airways to be processed and transported into tissues for presentation to lymphocytes. Hypotheses are that eosinophils are effective at presenting inhaled antigens to lymphocytes, that this eosinophil antigen processing and trafficking occur in vivo within the airways, that eosinophil high affinity IgE receptors function to enhance eosinophil antigen presentation of allergens, and that antigen presentation by eosinophils, perhaps based on their release of preformed, cytokines, skews Th2-mediated responses to inhaled antigens. Studies aim to define the capacity of human eosinophils in vitro 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 focus on the roles of eosinophils in propagating the chronic airway inflammation of asthma. Roles for eosinophils as antigen-presenting cells in sustaining allergic responses to inhaled particulate allergens would provide insights into the characteristically chronic nature of allergic diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI051645-04
Application #
6762385
Study Section
Special Emphasis Panel (ZAI1-NBS-I (M3))
Program Officer
Plaut, Marshall
Project Start
2001-09-30
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
4
Fiscal Year
2004
Total Cost
$382,500
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
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