The long-term objectives of this study are to characterize the cellular components of salivary gland-associated lymphoid tissue and define regulatory factors involved in the appearance, localization and development of immunocompetent cells in salivary glands.
The specific aims are: 1. to characterize and determine the origin of lymphoid cells present in salivary glands; 2. to define the mechanisms regulating lymphoid cell localization within salivary glands; and 3. to study the effect of cytokines on the development and function of immunocompetent cells in salivary gland tissues. Experiments will be conducted in the rat model, which has a well-characterized oral mucosal-associated immune system. Flow cytometry will be used to study phenotype expression in cells isolated from 'unimmunized' neonatal and adult major salivary glands. The impact of in vivo antigen perturbation on lymphocyte subset appearance in adult salivary gland tissues will also be assessed. The origin of lymphoid subsets in salivary glands will be studied using in situ labelling and adoptive transfer techniques. Lymphocyte-salivary gland interactions will be characterized for individual major salivary gland types in both adults and neonates using an in vitro binding assay. The phenotypes of adherent cells will also be determined. Inhibitor studies will be used to define the lymphocyte adhesion receptor and the epithelial cell ligand. A salivary gland tissue culture system will be used to assess the effect of IgA-enhancing cytokines on immunoglobulin and antibody production. Based on the in vitro culture data, selected cytokines will be tested for their capacity to enhance IgA immunoglobulin and antibody production in vivo. These effects will be correlated with changes in salivary gland lymphocyte subset distribution in stimulated animals. These studies will provide a more complete understanding of regulatory events governing salivary gland-associated lymphoid components and define new approaches to control mucosal immune responses in the oral cavity.
