The long-term goals of this project are to understand the immunobiology of asthma and allergic diseases. While our understanding of the role of Th2 responses in the pathogenesis of asthma has improved substantially over the past 10 years, our knowledge of the mechanisms that dampen Th2 biases inflammatory responses and that protect against the development of Th2 inflammation and the asthma remains rudimentary. The purpose of these studies is to examine allergic subjects in clinical trials of oral allergen immunotherapy before and after therapy, to determine the mechanisms that down-modulate Th2 responses, and to identify the cell types and molecules that participate in protective immune responses against Th2-biased inflammation. We will examine allergic individuals undergoing oral allergen immunotherapy with encapsulated cat allergen in clinical trials sponsored by Allergenics, Inc. We recently showed that treatment of allergic individuals with encapsulated allergen significantly reduced allergen-specific T cell proliferative responses. This suggests that treatment with oral allergen induced T cell tolerance, which we believe effectively protects against asthma and allergy, as we have previously shown in several mouse models of allergy and asthma. We now propose to examine a variety of parameters to identify the protective immune mechanisms that are activated by oral allergen immunotherapy. These parameters include assessment of T cell proliferation, T cell cytokine production, as well as gene expression profiling with cDNA microarrays. By comparing these parameters in allergic individuals before and after allergen immunotherapy we will begin to understand the mechanisms that protect against allergy and asthma. We will thereby develop a distinctive molecular portrait of the biology of, and identify specific genes and pathways important in, protective immunity. These studies therefore, are likely to lead to better methods and therapies that will induce protective immunity and allergen-specific tolerance, which will potentially cure patients with asthma and allergic diseases.
| Macaubas, Claudia; Wahlstrom, Jan; Galvao da Silva, Ana Paula et al. (2006) Allergen-specific MHC class II tetramer+ cells are detectable in allergic, but not in nonallergic, individuals. J Immunol 176:5069-77 |
