Possible Role of Gingival Epithelial Cells in Host Immune Response of Periodontal Disease Progression

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The purpose of the present research project was to clarify the possible role of gingival epithelial cells in host immune response of periodontal disease progression. Antigen presented by professional antigen-presenting cells (APC), which express both MHC class II and B7 costimulatory molecules, results in CD4+ T cell activation. In contrast, antigen presentation by MHC class II expressing non-professional APC which lack costimulatory molecules can render CD4+ T cells into a state of nonresponsiveness. In general, B7 costimulatory molecules are expressed by professional APC, such as macrophages or dendritic cells. Expression of MHC class II and B7-1 was detected on periodontal diseased human gingival epithelial tissue in situ by double color exposure confocal microscopy, but not in healthy gingival tissue. Also, two lines of rat gingival epithelial cells (GEC) demonstrated to constitutively expressed B7-1, but not B7-2 as analyzed by flow cytometry. By contrast, expression of MHC class II was only detected on both rat GEC klines after IFN-γ stimulation. Other rat non-professional APC such as endothelial cells or fibroblasts did not express B7-1 even after stimulation with IFN-γ. In order to elucidate the immunological significance of this ectopic B7-1 expression, antigen (Actinobacillus actinomycetemcomitans)-spedfic CD4+ Th1 T cell clones were cocultured with IFN-γ-/antigen-treated rat GEC. Consequently, the T cells became unresponsive to subsequent antigen-stimulation by professional APC as demonstrated by diminished proliferation. The induction of unresponsiveness was inhibited by anti-class II mAb or anti-CD80 mAb in the coculture of T clone cells and IFN-γ/antigen-treated GEC suggesting that GEC apparently present bacterial antigen, which resulted in T cell down regulation. These results suggest that ectopic expression of B7-1 by GEC may play a regulatory T cell to the commensal bacteria in the oral cavity in the context of a local inflammatory response.