Complex immune regulatory phenomena are involved in normal and pathological immune reactions. There are abundant immune regulatory cells in periodontal disease tissue in humans and rats. In addition to T suppressor type(Ts) cells, there are 2 types of functional T helper type cells in rodents and humans; Th1 and Th2 which appear to be intimately involved in the development of experimental periodontal lesions. Th2 cells appear to be protective when transferred as a clone into infected recipients. We have developed a model using A. actinomycetemcomitans (Aa) infected normal and congenitally atymic rats to study these phenomena. Currently, this is the only model available where the specific immunological manipulation required to study immune cellular aspects of periodontal disease can be performed. The long term objective of this proposed research will be to investigate the roles of specific host lymphoid cells in the establishment and maintenance of experimental periodontal disease in order to determine which elements are destructive and which elements are protective. This proposal will explore the effects of adoptive transfer of antigen-specific T cell subtype clones on experimental periodontal disease and explore the interactions necessary between the cell types in the genesis of experimental periodontal disease. Cell survival and the nature of the dynamics of cell involvement will be explored by analysis of immunological parameters and disease. Monoclonal antibodies for phenotype disclosure and functional assays such as Il-2 production will be used to recognize selected cell populations in recipient host tissues. Other indicators will be antibody formation (ELISA procedure), cell proliferation, and phenotypic analyses using flow cytofluorometry. Further subtype analyses, particularly of gingival cells will involve limiting dilution procedures coupled with phenotypic and functional analyses to determine precursor frequency of specific T cell subtypes. We will also investigate the homing of radiolabelled( 125IUDR) antigen specific cloned cells of various subtypes into periodontal lesions in infected rats over the course of lesion development. Labelled Aa specific Th1, Th2, and Ts clones and B cells will be traced in tissues by gamma counting and will be specifically localized by autoradiography of gingival tissue sections. This proposal holds promise for further understanding of the regulatory cell involvement in periodontal disease since definite correlations exist between the rodent systems and human disease.
Showing the most recent 10 out of 16 publications
