The objective of our research is to analyze the immune function of accessory cells in the lung and to relate these to immune responses triggered as a result of inhaled pathogens and foreign antigens. Accessory cells, during the induction of most immune responses, must express MHC class II antigens (Ia) on their surface and have the ability to endocytose, process and present antigen to T-cells.
The specific aims are to identify those cells in the Lewis rat lung which have the ability to present antigen ad to analyze the defect(s) which render the alveolar macrophage (AM) unable to effectively present antigen to T-cells. This will be accomplished by using native hen egg lysozyme (HEL) and peptide fragments containing the major T-cell epitope. The ability to present antigen will be measured by means of an immune T-cell proliferation assay. Double labelling immunogols techniques will use high affinity rabbit anti-FITC antibodies and monoclonal mouse anti-rat Ia antibodies to identify the cellular compartments through which FITC-HEL passes before presentation on the cell surface and to establish whether it becomes associated with Ia at any time within the cell. The nature of a putative binding activity for T cells on the AM surface will be examined. Cell isolation techniques will be used to isolate interstitial macrophages, dendritic cells, and alveolar type II pneumocytes to test for their ability to either express Ia constituitively or following stimulation with interferon-enriched lymphokine. They will be examined for their ability to present HEL antigen to HEL immune T-cells and to express interleukin I activity. Finally the interaction of these cells with immune T-cells will be examined in HEL-immunized Lewis rats challenged by the intratrached administration of soluble or insoluble HEL covalently linked to 15 nm gold particles. Results from these studies should lead to a better understanding of the adaptations AM have undergone that have resulted in their failure to present antigen effectively. They will also identify those cells in the lung which serve as competent antigen presenting cells.
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