Immune Conjugates of T-cells with Dendritic Cells in Periodontitis

Studies of periodontitis (PD) in gene knockout mice, in rats and in humans suggest that activated CD4+ T cells play an important role in the pathogenesis of PD and in alveolar bone loss. How T cell activation occurs and by what cells, however, is presently unclear. Our published human studies (Jotwani et al. 2001) used single immunoenzyme staining to reveal that in PD, immature CD1a+ dendritic cells infiltrate the gingival epithelium, while CD83+ mature dendritic cells (mDC), potent antigen presenting cells (APCs), infiltrate the CD4+-rich lamina propia. Objectives: 1) to identify the potential precursors of mDC in the human PD lesion in situ; 2) to determine whether direct contact between mDCs and T cells occurs in situ. Methods: cryostat-sectioned gingiva from humans with PD (n=5) and gingival health (n=5) were subjected to double immuno-enzyme and -fluorescence staining, using monoclonal antibodies against the Langerhans cell (LC)-specific marker Langerin, the mDC-specific marker CD83, and CD4. Control serial sections were stained with isotype matched antibodies. Slides were analyzed by image enhanced light and fluorescence microscopy and confocal laser scanning microscopy. Results: LCs do not associate with CD4+ T cells in the epithelium (epi); however, LCs do co-localize with mDC at the junction of epi and lamina propria, suggesting that LCs might be a source of mDC in human gingiva in PD. Further, mDC were surrounded by large clusters of CD4 + T cells in PD, and were observed in direct contact with T cells, as opposed to healthy gingival tissue in which sparse clustering of CD4 +T cells was observed. Conclusions: these studies suggest that Langerhans cells are a potential source of mature DCs in periodontitis and that mature DCs might be critical APCs in local T cell activation and possibly, in antigen-presentation in situ. Supported by NIH/NIDCR DE14160-01 and DE13154-01