LYMPHOKINE PROFILES IN ASTHMA AND ALLERGIC DISEASES

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Asthma is an inflammatory disease of the airways. After allergen exposure, IgE bearing cells, such as mast cells and basophils, are first activated. Later, T lymphocytes enter the airways, 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 profiles of mast cell, basophil and T cell subpopulations that may be involved in the generation of inflammation in asthmatic airways. One goal is to identify mast cell and basophil products that may contribute to bronchial inflammation. A second goal is to define the cytokine profile of peripheral blood and bronchoalveolar lavage (BAL) T cells from asthmatics and normal volunteers, to determine if indeed there is preferential trafficking of specific cytokine producing T cell subsets. Finally, we wish to characterize human NK1 T cells, which in mouse models of allergy play a key role in initiating Th2 polarized T cell responses. To date, we have found that human mast cells, including those in the lungs, produce and secrete IL-16, a chemotactic factor for CD4 T cells. IL-16 accounts for a majority of the CD4 T cell chemotactic activity secreted by mast cells. This trafficking of T cells to the allergen exposed lung has been examined by bronchoalveolar lavage, demonstrating a predominant Th1 profile. We have also identified a human analog of the previously described murine NK1 T cell, characterizing their unique TCR usage of V-alpha-24, V-beta-11. IL-4 was expressed in NK1 T cells at a 6 fold greater level relative to mainstream T cells and was uniquely found in cells of a Th0 dual expressing phenotype. Using similar techniques, we have shown that basophils obtained from allergic asthmatics are the predominant source of IL-4 in peripheral blood mononuclear cells.