Allergic bronchopulmonary aspergillosis (ABPA) is an immune hypersensitivity disease that is a complication in patients with either asthma or cystic fibrosis. It results from the allergic response to Aspergillus antigens that colonize the respiratory tracts in patients compromised by either of the above mentioned diseases. Our studies focus on the HLA class II molecules and associated Af antigens that activate and direct CD4+ T cells to produce the cytokines IL-4, IL-5, and IL-13 which lead to an allergic response and disease. A major goal of this work is to understand how the HLA class II molecules in association with antigen trigger intracellular signals that program T cells to produce particular cytokine profiles.
Identification and characterization of the immune response to the smallpox vaccine. Bioterrorism has been pushed to the forefront by the tragic events of September 11, 2002. Smallpox is a likely candidate virus to be used by terrorists because of the lack of immunity in a large number of the global population. In the event of a bioterrorist attack mass vaccination would have to take place using the best possible vaccines that are safe and rapidly effective. It is not clear that the existing smallpox vaccines meet these requirements. Because of historical reasons little is known regarding the cellular and molecular mechanisms that underlie the immune response to the smallpox virus. Our laboratory studies this response in lymphocytes derived from vaccinated volunteers. Our focus is to map the critical viral epitopes that immune T cells target in successful immune responses. In addition we identify and characterize the phenotype and function of the T cells that are directed to these epitopes. Ultimately this information is needed for the design of new safe and effective smallpox vaccines.
Regulation of IL-1ß in keratinocytes. Chloracne is a severe debilitating inflammatory skin disease that is promoted by the dysregulated production of the cytokine, IL-1. A number of agents, most prominently bacterial components, are responsible for the production and release of IL-1. Although not well studied, there are several reports that halogenated aromatic hydrocarbons (HAHs), which are implicated in some inflammatory diseases, also stimulate IL-1 in several different tissues. The most recognizable and potent member of this class of compounds is 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD). Our work has shown that TCDD triggers IL-1 production in differentiated keratinocytes, a major cell type in skin, and this response is mediated by the aryl hydrocarbon receptor (AhR). This signaling pathway acting on the IL-1 gene to promote transcription appears to be through a novel mechanism. Our goals are to identify and characterize the transcription factors responsible for the activation of IL-1 transcription through this novel mechanism.