Characterization of Th2 memory in mouse allergic asthma

CD4 T cells produce cytokines that recruit inflammatory cells to the lungs and promote airway hyperreactivity, mucus hypersecretion, and IgE, which in combination characterize allergic asthma. Though allergen inhalation in sensitized individuals induces disease exacerbations, little is known about allergen-specific memory CD4 cells and where they reside during disease remission. Our previous results show that mice immunized with soluble and aerosolized antigen, develop allergic asthma with focal peripheral lung inflammatory infiltrates that closely resemble human lesions. These infiltrates persist in the lungs for the lifetime of mice recovered from acute disease in the absence of further antigen exposure. However, upon antigen stimulation, lung CD4 cells act rapidly to produce Th2 cytokines resulting in disease relapses over one year after the last antigen exposure. In addition, antigen-specific cells persist in the spleen demonstrating that long-lived local and systemic memory Th2 cells produce a rapid and effective response, which characterizes immunological memory. Using this model we have a unique opportunity to characterize local lung memory Th2 cells and to explore whether chemokine-chemokine receptor interations influence the maintenance of memory Th2 cells. Our proposal focuses on two major issues: 1). phenotypic and functional characterization of allergen-specific Th2 memory cells in lungs and 2). investigating the mechanisms underlying the maintenance of memory Th2 cells. While long-lived immunity is vital for protection against pathogens, allergen-specific memory is detrimental. Understanding the mechanisms underlying immunological memory has implications for vaccine development, tumour immunology, allergy, autoimmunity and transplantation.