M CELL UPTAKE AND CYTOARCHITECTURE IN PEYER'S PATCHES

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Our objectives are to define the functions and regulation of intestinal lymphoid organs. These goals are relevant to oral immunization, intestinal infection, M cell uptake of antigens and particles, including HTLV III, and to pathogenesis of immunologic diseases. The first specific aim is to define uptake and transport of particulate microbial antigens, tracer particles, and liposomes in animal models. We propose to study the entry route(s) of chlamydia organisms through small intestinal and rectal lymphoid follicle epithelia and the mechanism of transport of these organisms into lymphoid tissues. The consequences of chlamydia-induced hyperplasia of lymphoid follicles on M cell proliferation and uptake of luminal particles will be evaluated. Modulation of antigen uptake from the intestinal lumen by secretory IgA will be assessed using cholera vibrios and also microspheres with and without IgA antibody. Liposomes containing 3H labeled proteins or colloidal gold particles will be used to evaluate peroral delivery of antigens and drugs through M cells. Migration pathways of mononuclear leukocytes will be traced to determine whether cells can carry antigen from the intestinal lumen into Peyer's patches. The second specific aim is to investigate modulation of Peyer's patch cytoarchitecture and function by antigenic stimulation and by depletion of regulatory lymphocyte subsets in normal mice and in a mouse model of systemic lupus erythematosus (SLE). The mechanisms by which intestinal antigen stimulation regulates surface Ig isotype switching in Peyer's patches will be evaluated by immunolabeling and fluorescence activated cell sorting (FACS). Monoclonal antibodies will be used to deplete lymphocyte subsets; the effects of subsequent changes in immunoregulatory cells on the cytoarchitecture of mucosal lymphoid organs will be assessed by immunolabeling in normal mice and in autoimmune mice in which helper T cell depletion treats SLE.