Asthma is the most common chronic illness in developed countries. Despite advances in our understanding of its pathogenesis and therapy, the morbidity and mortality associated with asthma are increasing both in the United States and worldwide. The inflammatory aspects of the disease are complex with mast cells, dendritic cells, T- and B-lymphocytes, and eosinophils all playing important roles in the pathogenesis of asthma. An increase in eosinophils and T lymphocytes in the bronchial mucosa and bronchoalveolar lavage (BAL) fluid is a characteristic feature of the inflammatory response in patients with asthma. Increased numbers of activated T cells in bronchial mucosa and peripheral blood in asthma patients appear to correlate with the severity of the disease. A unique class of T lymphocytes composed of T cell receptors (TCR) with gamma/delta chains has been identified in the mucosal immune system. These gamma/delta T cells appear to have a role in immunosurveillance of epithelial cell surfaces, including the intestinal and respiratory tract. Gamma/delta T cells have a non MHC restricted antigen specificity as compared to the classical response of alpha/beta T cells, can eliminate infected epithelial cells before the adaptive T cell immune system responds, and they have immunregulatory properties such as selectively suppressing IgE responses. Thus, gamma/delta T cells protect the epithelium from invading pathogens and from tissue damage associated with the adaptive T cell response and inflammation. Gamma/delta T cells have been identified throughout the human airway epithelium and are occasionally noted in the submucosal vessels. We hypothesize that in the ovalbumin induced allergic asthma model in mice there is a selective expansion of """"""""proinflammatory"""""""" gamma/delta T cells in the early stages of the allergic reaction which aid in the breaking of the tolerant non-allergic state and contributes to the inflammatory response. Further in the chronic tolerant stage of this model, we hypothesize that the gamma/delta T cell population in the lung has returned to its """"""""more normal"""""""" array of cells, predominantly of the """"""""suppressor"""""""" type which downregulate the inflammatory response. Therefore, the specific aims of this project are to: 1) demonstrate, in normal wild type mice that the development of ovalbumin-induced allergic asthma alters respiratory tract gamma/delta T cell and alpha beta T cell populations, 2) determine if the progression of disease and/or cellular characteristics are altered in gamma/delta T cell deficient animals in this model, 3) determine if the transfer of gamma/delta T cells isolated from animals at various stages (and tissue locations) of the ovalbumin model can alter the development of the ovalbumin induced response in normal wild type mice.
Showing the most recent 10 out of 18 publications
