CD8+ Foxp3+ T Cells Affect Alveolar Bone Homeostasis via Modulating Tregs/Th17 During Induced Periodontitis: an Adoptive Transfer Experiment.

Periodontitis is a dysbiotic bacteria-mediated disease characterized by periodontal inflammations and alveolar bone damage. Its mechanisms were complicated, involving an inflammation-mediated bone destruction. We sought to determine roles and rules that CD8+ regulatory T cells (CD8+ Tregs) affect alveolar bone homeostasis during periodontitis. Presence of CD8+ Tregs in the gingiva, cervical lymph nodes (CLNs), and spleens of healthy or periodontitis animals was analyzed. CD8+ regulatory T cells from periodontitis animals were sorted by magnetic-activated cell sorting and fluorescent-activated cell sorting technique, subsequently injected into recipient animals to set adoptive transfer model. We induced experimental periodontitis on transfer models and equal number healthy animals. Four weeks later, their alveolar bone loss and osteoclast coverage length were measured. We also detected CD8+ Tregs, CD4+ T cell, CD4+ Tregs, Th17 cell, and IL-1β, IL-6, IL-10, IL-17A, RANKL, TGF-β expression in the gingiva, CLNs, and spleen to illustrate possible working mechanism of CD8+ regulatory T cells. Periodontitis does not induce significant change on proportion or amount of CD8+ Tregs. Adoptive transfer of CD8+ Tregs reduces alveolar bone destruction and osteoclast formation. In addition, experimental periodontitis increases percentage of Th17 cells and decreases CD4+ Tregs in the gingiva and CLNs. More IL-1β, IL-6, IL-17A, and RANKL, and less IL-10 and TGF-β are also detected in the gingiva and CLNs from animals with periodontitis than the one from healthy animals. Adoptive transfer of CD8+ regulatory T cells remedies all above pathological change effectively. We did not find any significant difference in spleen, regardless group and detected items. Outcomes of present study clarify function that CD8+ regulatory T cells affect alveolar bone homeostasis, and disclose its possible working mechanisms. CD8+ regulatory T cells protect alveolar bone via reducing osteoclastogenesis and modulating local immune response.