gamma delta T Cells Differentially Regulate Bone Loss in Periodontitis Models

gamma delta T cells are nonclassical T lymphocytes representing the major T-cell population at epithelial barriers. In the gingiva, gamma delta T cells are enriched in epithelial regions adjacent to the biofilm and are considered to regulate local immunity to maintain host-biofilm homeostatic interactions. This delicate balance is often disrupted resulting in the development of periodontitis. Previous studies in mice lacking gamma delta T cells from birth (Tcrd(-/-) mice) examined the impact of these cells on ligature-induced periodontitis. Data obtained from those studies proposed either a protective effect or no impact to gamma delta T cells in this setting. Here, we addressed the role of gamma delta T cells in periodontitis using the recently developed Tcrd-GDL mice, enabling temporal ablation of gamma delta T cells. Specifically, the impact of gamma delta T cells during periodontitis was examined in 2 modalities: the ligature model and the oral infection model in which the pathogen Porphyromonas gingivalis was administrated via successive oral gavages. Ablation of gamma delta T cells during ligature-induced periodontitis had no impact on innate immune cell recruitment to the ligated gingiva. In addition, the number of osteoclasts and subsequent alveolar bone loss were unaffected. However, gamma delta T cells play a pathologic role during P. gingivalis infection, and their absence prevented alveolar bone loss. Further analysis revealed that gamma delta T cells were responsible for the recruitment of neutrophils and monocytes to the gingiva following the exposure to P. gingivalis. gamma delta T-cell ablation also downregulated osteoclastogenesis and dysregulated long-term immune responses in the gingiva. Collectively, this study demonstrates that whereas gamma delta T cells are dispensable to periodontitis induced by the ligature model, they play a deleterious role in the oral infection model by facilitating pathogen-induced bone-destructive immune responses. On a broader aspect, this study highlights the complex immunopathologic mechanisms involved in periodontal bone loss.

Automated summary

Gamma delta T cells play various roles in the development of periodontitis, with different impacts in different models. While they are important in maintaining host-biofilm homeostasis, they can also contribute to pathological responses under specific conditions.