The long-term objectives of this study are to define the specific regulatory processes governing ocular mucosal-associated immune responses and provide basic information applicable to the design of clinically relevant immunization protocols. The overall hypotheses to be tested are; 1. that antigen dissemination and the traffic of specific lymphoid populations play major roles in the induction of tear IgA antibody responses following ocular topical immunization; 2. that certain cytokines play key roles in the induction and expression of tear IgA antibodies; and 3. that specific lymphocyte receptors and acinar cell ligand molecules mediate the selective localization of lymphoid populations within lacrimal gland tissues.
The specific aims to test these hypotheses are:
AIM 1. To define the regulatory events leading to IgA antibody induction and expression in tears after ocular topical stimulation.
This aim will compare the kinetics of antigen distribution and examine cell traffic to lacrimal gland and conjunctiva following ocular topical immunization, AIM 2. To determine the role of cytokines in the induction and expression of tear IgA antibodies.
This aim will determine the levels and functional significance of endogenous cytokines in ocular mucosal tissues and test the use of biodegradable microparticles as an ocular delivery vehicle for antigen and/or IgA enhancing cytokines.
Aim 3. To characterize the molecules responsible for lymphocyte interactions with lacrimal gland acinar epithelial cells.
This aim will examine the molecular structure of the lymphocyte receptor and determine the biochemical nature of the acinar epithelial cell ligand. Experimentation will use the rat model, which has a well-characterized ocular mucosal immune system. To achieve these aims, light and electron microscopy, cell isolation, cell and organ fragment cultures, flow cytometry, hybridoma production and in vitro adherence methods will be employed in conjunction with immunochemical, biochemical and molecular analyses. Overall, these investigations will provide a more complete understanding of the events involved in the regulation of ocular mucosal-associated antibody induction and identify new approaches to generate and control immune responses at the ocular surface.

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Wayne State University
United States
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