IADR Abstract Archives
Human Effector Memory T Cells in Healthy Gingiva and Periodontitis
Objectives: Periodontal disease is a chronic inflammatory disease which is triggered by oral pathogens and gradually leads to irreversible alveolar bone resorption and ultimately tooth loss. T lymphocytes contribute to inflammation and bone resorption in periodontal disease. Here, we characterize T cell naïve and memory subsets in human periodontal disease.
Methods: Human gingival tissue biopsies were obtained from sites of gingival health and periodontitis. Gingival tissue was also collected after treatment of periodontitis. We used flow cytometry analysis to determine the distribution of naïve (CCR7+CD45RA+), central memory (TCM, CCR7+CD45RA-), effector memory (TEM, CCR7-CD45RA-; TEMRA, CCR7-CD45RA+) and resident memory T cells (TTRM, CCR7+CD45RA-CD69+) within the CD4+ and CD8+ populations in gingival tissues.
Results: The majority of CD4+ cells in gingival tissues are non-recirculating TTRM cells, with a minor fraction of naïve and TCM cells. In periodontitis, the proportion and the absolute number of recirculating TEM cells increases, while the tissue resident population decreases. This was most evident in donors with poorly controlled oral hygiene and less so in donors who had been treated for periodontitis.
Conclusions: The influx of recirculating TEM cells into the gum may reflect an ongoing systemic immune response, while the ratio of tissue resident versus recirculating memory cells may depend on the inflammatory status of the disease. Interestingly, in a rat model of periodontitis, suppressing TEM cells with a specific inhibitor of the voltage-gated KV1.3 channel reduces bone resorption.This raises the possibility of developing therapeutic strategies for periodontitis to inhibit TEM cells and reduce bone resorption that complete standard-of-care therapies to improve oral hygiene.
Methods: Human gingival tissue biopsies were obtained from sites of gingival health and periodontitis. Gingival tissue was also collected after treatment of periodontitis. We used flow cytometry analysis to determine the distribution of naïve (CCR7+CD45RA+), central memory (TCM, CCR7+CD45RA-), effector memory (TEM, CCR7-CD45RA-; TEMRA, CCR7-CD45RA+) and resident memory T cells (TTRM, CCR7+CD45RA-CD69+) within the CD4+ and CD8+ populations in gingival tissues.
Results: The majority of CD4+ cells in gingival tissues are non-recirculating TTRM cells, with a minor fraction of naïve and TCM cells. In periodontitis, the proportion and the absolute number of recirculating TEM cells increases, while the tissue resident population decreases. This was most evident in donors with poorly controlled oral hygiene and less so in donors who had been treated for periodontitis.
Conclusions: The influx of recirculating TEM cells into the gum may reflect an ongoing systemic immune response, while the ratio of tissue resident versus recirculating memory cells may depend on the inflammatory status of the disease. Interestingly, in a rat model of periodontitis, suppressing TEM cells with a specific inhibitor of the voltage-gated KV1.3 channel reduces bone resorption.This raises the possibility of developing therapeutic strategies for periodontitis to inhibit TEM cells and reduce bone resorption that complete standard-of-care therapies to improve oral hygiene.