Therapeutic Potential of TCRαβCD4CD8T Cells in Periodontitis.

Abstract

Periodontitis, a pervasive chronic inflammatory disorder, is distinguished by the progressive degradation of periodontal tissues and alveolar bone. Despite remarkable progress in understanding the pathogenesis of periodontitis, the involvement of TCRαβCD4CD8T cells, also known as double-negative T (DNT) cells, in the pathophysiology of this disease has not been thoroughly investigated. In this study, we observed a significant reduction in the frequency of TCRαβDNT cells within the gingival tissues of patients afflicted with periodontitis when compared with healthy individuals. Employing a murine model, we demonstrated that the therapeutic administration of TCRαβDNT cells resulted in a reduction of alveolar bone resorption and a decrease in inflammatory biomarkers, with the most significant effects observed at lower cell doses. Histological examination and gene expression analysis revealed a notable attenuation in the expression levels of proinflammatory cytokines. Furthermore, transcriptomic profiling elucidated the downregulation of pathways associated with neutrophil activation and interleukin-17 signaling, which are critical in the inflammatory cascade of periodontitis. Both in vitro and in vivo experiments underscored the pivotal role of perforin in TCRαβDNT cells, which is essential for modulating periodontal inflammation and preventing alveolar bone loss. Collectively, our findings suggest that TCRαβDNT cell therapy may represent a promising novel therapeutic strategy for periodontitis, providing valuable insights into the development of innovative treatment modalities for this prevalent oral health condition.