Innovative Therapeutic Strategies: Tcrαβ+Cd4-Cd8- T Cells In Periodontitis

To evaluate the proportion of TCRαβ+CD4-CD8- T cells in periodontitis and their potential as therapeutic targets by analyzing changes in these cells in human and mouse tissues and investigating their effects on inflammation and bone loss. Flow cytometry and immunofluorescence were used to analyze TCRαβ+CD4-CD8- T cells in severe chronic periodontitis patients' vs. healthy controls' gingival tissues. Mouse models received low- or high-dose injections of these T cells. Micro-CT, histology, and gene expression assessed their effects on alveolar bone destruction and inflammation. Transcriptomics identified differentially expressed genes and pathways. In vitro co-culture experiments clarified the mechanisms. The study was approved by the Ethics Committee of Beijing Friendship Hospital. TCRαβ+CD4-CD8- T cells were significantly reduced in periodontitis patients (9.6±2.35%) compared to healthy controls (14.42±2.2%, p<0.05). Low-dose T cell treatment in mice significantly reduced alveolar bone resorption and inflammation. Histological and RNA analysis showed decreased expression of genes related to neutrophil responses and IL-17 signaling. Transcriptomic analysis indicated downregulation of neutrophil activation and chemotaxis pathways. Perforin was identified as a key factor in the immunoregulatory effects of these T cells, which also promoted neutrophil apoptosis and reduced IL-1β production and neutrophil extracellular traps (NETs) in vitro. TCRαβ+CD4-CD8- T cell therapy effectively mitigates periodontal inflammation and bone destruction by modulating neutrophil activity and IL-17 signaling pathways, offering a novel therapeutic approach for periodontitis.