The long-range objectives of the Forsyth Department of Immunology are to explore the ability of mucosal and systemic immune mechanisms to modulate or exacerbate diseases of the oral cavity and to use its findings to ameliorate these diseases. Department members focus on major oral infections and autoimmune diseases.
To interfere with pathogens that cause dental caries, inductive sites for mucosal immunity in the head and neck, including nasal-associated lymphoid tissue, tonsils, minor salivary glands and distant sites, are being evaluated as routes for delivery of vaccines, principally against dental caries. The Department is investigating novel delivery vehicles and biological adjuvants, applied with antigen at these sites, for their ability to enhance immunity at the oral mucosa and at other sites.
Other approaches to preventing oral disease include identifying vaccine targets associated with components of the molecular pathogenesis of dental caries. Subunit vaccines based on functional epitopes of Streptococcus mutans glucosyltransferases (GTF) are being developed and tested, as are conjugate and recombinant vaccines. Glucan binding proteins (GBP), important in cariogenic dental biofilm formation, have been cloned and sequenced, and their functional epitopes have been identified. GTF and GBP epitopes, once identified, are incorporated into vaccines, which are evaluated for protective potential.
The Department emphasizes research in the interplay between the host response to periodontopathic bacteria and the development of periodontal diseases in both human and animal model systems. The main focus of these studies is to characterize the functional potential of immune cells found in periodontal lesions, with particular emphasis on T cells' role in regulating responses and contributing to disease. Both Th1 T cells and B cells produce cytokines that can be directly linked to the bone resorption associated with periodontal disease. These studies contribute to the new discipline of osteoimmunology, which links the immune system to bone resorption and bone apposition. Anergy (lack of immune response) may be inducible in T cells in periodontal lesions when antigens are presented in the absence of costimulatory molecules. The Department is actively exploring this and other potentially protective immune mechanisms as a means of interfering with destructive T cell traffic into periodontal lesions. Research topics include the role of T regulatory cells and host-derived small molecules, called "defensins," in periodontal disease.
Another Department focus is autoimmune disease in the oral cavity, studied in the non-obese diabetic (NOD) mouse. This model for Sjögren's syndrome has been used to show that autoantibodies can induce the decreased salivary secretion that characterizes this condition. Parallels between the autoantibody repertoires of humans with Sjögren's syndrome and those of diseased NOD mice have been demonstrated, providing a window on pathogenic processes common to the two species. Identifying the antigenic targets of these autoantibodies and the mechanisms by which antigen-antibody interaction results in pathology is a particular interest. In addition, the expression of cloned autoantigens has the potential to yield specific diagnostic tests for clinical use. The Department is also prospectively studying the roles of cytokines and inflammatory cells in the pathogenesis of Sjögren's syndrome.
Martin A. Taubman, D.D.S., Ph.D.
Daniel J. Smith, Ph.D.
Toshihisa Kawai, D.D.S., Ph.D.
Xiaozhe Han, D.D.S., Ph.D.
