Asthma is an inflammatory disease of the airways. In allergic asthma, mast cells are first activated. T lymphocytes then enter pulmonary tissues and play a key role in regulating the inflammatory response through the elaboration of cytokines such as IL-4, IL-5 and IFN-g. This project is directed to an examination of the cytokine profiles of mast cell and T cell subpopulations that may be involved in the generation of inflammation in asthmatic airways. One goal is to define the cytokine profile of peripheral blood and bronchoalveolar lavage (BAL) T cells from asthmatics and normal volunteers, to determine if there is preferential trafficking of specific cytokine producing T cell subsets. A second goal is to identify mast cell products that may attract lymphocytes to sites of pulmonary inflammation. Finally, we wish to characterize NK1.1 or natural T (NT) cells in this response. To date we have found that human mast cells, including those in the lung, produce and secrete IL-16, or lymphocyte chemotactic factor. The distribution of lymphocytes then arriving into the lung as assessed by bronchoalveolar lavage following allergen challenge is uneven between the Th1 and Th2 subsets. We have also found that the human NK1 analog expresses a unique TCR pair of Va24 and Vb11, as well as the NK associated marker CD56. Purified human NT cells express a single TCRa chain gene rearrangement consisting of Va24-JaQ, and have greater frequencies of cells producing both IFNg and IL-4 production, with CD4+ NT cells demonstrating a 6-fold greater frequency of IL-4 producers relative to mainstream CD4+ NT cells. These data are consistent with a role in priming the immune response toward the Th2 phenotype.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000709-04
Application #
6160711
Study Section
Special Emphasis Panel (LAD)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
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