Abstract

In our previous studies, we examined the molecular mechanisms of adhesive interactions between lymphocytes and human gingival fibroblasts (HGF) that occur at inflammatory gingival connective tissues. We found that activation of lymphocytes led to their increased adhesiveness to HGF, and that adhesion pathways involving at least VLA integrins, LFA-1/ICAM-1, and CD44/hyaluronate play crucial roles in the binding of activated lymphocytes to HGF. Furthermore, possible activation of HGF by adhesive interactions with lymphocytes was examined by monitoring the inflammatory cytokine expression. IL-1 and IL-6 mRNA expression in the HGF was increased when HGF directly interacted with lymphocytes. These results strongly suggest that adhesive interaction between these heterotypic cell types transduces activation signals into HGF that induce an increase in inflammatory cytokine mRNA expression. Recently, we examined by monitoring the expression of CD13 (aminopeptidase N) whether the direct interactions between lymphocytes and HGF can also stimulate the lymphocytes. Peripheral blood T cells (PBT) which had been cultured in the presence or absence of PMA were added to the HGF monolayers. After incubation, the PBT were harvested and CD13 expression on the cell surfaces was analyzed by flow cytometry. Furthermore, the presence of CD13 positive T cells in inflamed gingival tissues was also examined in vivo. Interestingly, CD13 expression was induced on PMA-activated PBT only when they were cultured on HGF. When HGF and PMA-activated PBT were cultured in the same well but separated by a membrane, no expression of CD13 on the PBT was observed. In addition, CD13 positive T cells, which were not detected in PBT of the same patients, were isolated from gingival tissues. These results indicate that direct interactions with HGF were essential for the induction of CD13 expression on T cells, which were observed in periodontitis lesions.

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