Background: Periodontitis, a chronic inflammatory disease of the periodontium, is characterized by osteoclast-mediated alveolar bone destruction. Gingival fibroblasts (GFs) present in the bone-lining mucosa have the capacity to activate the formation of osteoclasts, but little is known about which local immune cells (co-)mediate this process.

Objective: The aim of this study was to investigate the cellular interactions of GFs with immune cells, including the contribution of GFs to osteoclast formation and their possible role in the proliferation of these immune cells. We also investigated the expression of adhesion molecules and the inflammatory cytokines that are evoked by this interaction.

Results: After 21 days, comparable numbers of multinucleated cells (osteoclasts) were found in GF-PBMC and GF-monocyte cocultures. Remarkably, a predominance of CD3+ T cells was immunohistochemically detected in GF cocultures with PBLs and PBMCs for 21 days that frequently interacted with osteoclasts. Significantly more T, B (CD19+), and NK (CD56+CD3-) cells were identified with multicolor flow cytometry in both GF-PBMC and GF-PBL cocultures compared to monocultures without GFs at all time points. Lymphocyte retention is likely mediated by LFA-1 expression, which was significantly higher in GF-PBL cultures compared to GF-monocyte cultures. Thereby, high tumor necrosis alpha cytokine expression was only observed in the GF-PBMC cultures, indicating that this tripartite presence of GFs, monocytes, and lymphocytes is required for such an induction. Carboxyfluorescein succinimidyl ester-labeling showed that only the CD3+ cells proliferated in presence of GFs.

Conclusion: This study demonstrates a novel role for GFs in the survival, retention, and selective proliferation of lymphocytes.