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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE009658-10
Application #
6176840
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Zhang, Guo He
Project Start
1991-08-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2002-07-31
Support Year
10
Fiscal Year
2000
Total Cost
$235,864
Indirect Cost
Name
Wayne State University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
O'Sullivan, N L; Skandera, C A; Montgomery, P C (2001) Lymphocyte lineages at mucosal effector sites: rat salivary glands. J Immunol 166:5522-9
Montgomery, P C; Rafferty, D E (1998) Induction of secretory and serum antibody responses following oral administration of antigen with bioadhesive degradable starch microparticles. Oral Microbiol Immunol 13:139-49
O'Sullivan, N L; Skandera, C A; Montgomery, P C (1996) The specificity of adhesive interactions between rat lymphocytes and salivary gland epithelia. Cell Immunol 169:142-51
Montgomery, P C; Skandera, C A; O'Sullivan, N L (1996) Phenotypic profiles of lymphocyte populations isolated from rat major salivary glands. Oral Microbiol Immunol 11:248-53
O'Sullivan, N L; Montgomery, P C (1996) Lymphocyte adhesive interactions with cultured parotid salivary gland epithelial cells from rats. Oral Microbiol Immunol 11:337-42
Rafferty, D E; Montgomery, P C (1995) The effects of transforming growth factor-beta and interleukins 2, 5 and 6 on immunoglobulin production in cultured rat salivary gland tissues. Oral Microbiol Immunol 10:81-6
O'Sullivan, N L; Montgomery, P C (1993) In vitro adherence of rat lymphocytes to salivary gland epithelia. Oral Microbiol Immunol 8:188-93