Cytokine Profiles In Asthma And Allergic Diseases

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Abstract

Allergic diseases, such as asthma, allergic rhinitis and eosinophilic gastroenteritis, are inflammatory diseases of the mucosa. After allergen exposure, IgE bearing cells, such as mast cells and basophils, are first activated. Later, T lymphocytes enter the mucosa, are activated by allergen and play a key role in regulating this inflammatory response through the elaboration of cytokines such as IL-4, IL-5 and IFN-gamma. This project seeks to examine the cytokine and mediator profiles of mast cell, basophil and T cell subpopulations that may be involved in the generation of inflammation in allergic diseases. We have developed sensitive intracellular cytokine assays to measure allergen specific T cell cytokine responses with a fidelity heretofore not possible. Using these methods, we have shown that allergen specific T cells are predominantly of the classic Th2 phenotype, and that on the single cell level IL-4, IL-5 and IL-13 are highly co-expressed. Furthermore, heterogeneity of these cytokine producing Th2 cells has been, suggesting the possibility that specific diseases entities or inflammatory processes are the result of preferential differentiation of distinct cytokine producing Th2 cells. Specific subsets of allergen specific memory T cells have be identified and investigations into the factors promoting and inhibiting these subsets are being made. A thorough understanding of the biology of these pro-allergic inflammatory T cells is needed as a step in the development of therapeutic approaches to blocking the differentiation and function of these cells. Additionally, we have extended our previous work with IgE receptor (FceRI) bearing antigen presenting cells and have identified a subset of monocytes that express FceRI. FceRI expression by this subset correlated to serum IgE concentration and was reduced by therapeutic administration of anti-IgE. These results further define the role of FceRI and IgE in antigen presentation, and suggest that via this mechanism, anti-IgE therpeutics may have an effect on allergen specific T cell activation.