The long-term objectives of this project are to characterize the regulatory events affecting lymphoid cell interactions, composition and traffic as well as immune responses within salivary gland tissues. The overall hypotheses to be tested are: that specific epithelial cell adhesion (or ligand) molecules mediate the selective localization of lymphoid populations within individual salivary gland tissues; that delivery of antigen/cytokine signals to specific mucosal inductive sites will potentiate IgA antibody expression in saliva and that the localization of specific lymphoid populations within major salivary glands plays a role in the development of salivary IgA antibody responses.
The specific aims are: 1. To isolate and characterize the epithelial cell adhesion (or ligand) molecules mediating lymphocyte retention within salivary gland tissues.
This aim will determine the structure of the epithelial cell adhesion (or ligand) molecules from individual salivary glands and characterize the mechanism by which these molecules mediate lymphocyte retention within glandular tissues. 2. To study the effects of mucosal inductive site antigen/cytokine delivery on the potentiation of IgA antibody responses.
This aim will test the ability of bioadhesive degradable starch microparticles and the comparative capacity of poly(DL- lactide-co-glycolide) (PLG) and cholera toxin B-PLG microparticles to deliver mucosal inductive site antigen/cytokine signals that will potentiate IgA antibody responses in saliva and individual salivary glands. 3. To determine if the localization of specific lymphoid subpopulations plays a role in the development of IgA antibodies in individual salivary gland tissues.
This aim will test the effects of mucosal immunization on glandular lymphocyte distribution and traffic to individual salivary glands. Investigations in the rat model will utilize biochemical and immunological approaches in conjunction with cell and tissue culture systems, motility and adherence assays, cell isolation and flow cytometry as well as in situ and adoptive transfer techniques. These studies will define new strategies which will allow optimal manipulation and utilization of salivary-associated lymphoid components for immune- mediated host defenses in the oral cavity.
