Asthma is characterized pathologically by the development of mucosal inflammation. The importance of bronchial inflammation in the pathogenesis of asthma remains poorly understood. Recent reports suggest that the T cell may play an important role in mediating this inflammation through the secretion of cytokines. A murine model of pulmonary inflammation will be used to study the role of the T cell in allergic pulmonary inflammation. The model is characterized by: l) the production of antigen specific IgE and IgG responses, 2) pulmonary inflammation consisting of eosinophils, neutrophils, monocytes and lymphocytes 3) the development of late-phase pulmonary responses and 4) the development of airway hyperresponsiveness. A unique series of bispecific monoclonal antibodies have been developed that are specifically designed to target activated T cells and T cell subsets. These reagents will be used to examine the role of the T cell in generating pulmonary inflammation, late-phase pulmonary reactions and airway hyperresponsiveness in the murine model. We will address the following specific questions: l. How does the development of antigen-specific T cell responses correlate with late-phase reactions and airway hyperresponsiveness following antigen challenge in this model? 2. Does T cell targeting at the time of antigen challenge, diminish pulmonary inflammation, late-phase reactions and airways hyperresponsiveness in appropriately immunized mice? 3. Can adoptive transfer of antigen-specific T cell clones into naive mice, followed by antigen challenge, induce pulmonary inflammation, late- phase pulmonary reactions and airway hyperresponsiveness or does it require the development of antigen-specific humoral responses? 4. Can the use of anti-T cell immunomodulating agents, administered in the presence of antigen, induce humoral unresponsiveness to antigen and T cell anergy in this model? 5. What are the respective roles of antigen-specific humoral and cellular responses in the development of pulmonary inflammation in this model?
