ORAL EPITHELIUM: ACTIVE ROLE IN LOCAL IMMUNE RESPONSE

Periodontal disease is ubiquitous. As a major cause of tooth loss it represents an economic and social burden on the individual and on society. The goal of this project is to define the role of the gingival epithelium in the pathogenesis of periodontal disease by studying the mechanisms underlying the interaction between epithelial cells and the immune system. Attention will be focused on the epithelial Langerhans cells (LC). Specifically, the expression of T-6, a membrane differentiation antigen of immature thymocytes, by LC will be studied. By indirect immunofluorescence staining of gingival biopsies using OKT6 monoclonal antibody, the frequency of T-6 expressing LC in different patient groups will be compared. Endogenous labelling of T-6 will be performed in order to determine whether LC synthesize T-6 or if it is synthesized by some other cell and is cytophilic for LC. LC will be cultured in media containing radioactively labelled amino acids. The LC will then be lysed and T-6 will be immunopercipitated and electrophoretically isolated. Incorporation of the label into the T-6 molecule will indicate that it was synthesized by LC. A series of co-cultivation experiments will be done to increase understanding of the mechanisms by which LC are induced in the epithelium to express T-6. LC precursors will be co-cultivated with epidermal cultures (EC) in an attempt to induce T-6 expression in vitro. Similarly, LC will be cultured in media harvested from EC to determine if induction is mediated by soluble factors. Induction of T-6 by co-cultivation with EC will also be attempted in immature pre-T-6 thymocyte populations to demonstrate similarity between phenomena in the epithelium and thymus. Determination of the functional significance of T-6 expression by LC requires a syngeneic experimental system. Since TL antigen, the murine homolog of T-6, is expressed by murine LC, a mouse system will be developed. TL has been well studied in the mouse, and 6 allelic forms are known. Experiments using chimeras of strains of different allotypes should provide further information on the origin and function of the LC. This murine model should also allow the study of the function of LC T-6.