Cytokine responses of CD4+ T cells and NKT cells to periodontitis‐associated bacteria in individuals with or without periodontitis

Abstract

AbstractAimPeriodontitis is an inflammatory disease driven by opportunistic bacteria including Porphyromonas gingivalis and Fusobacterium nucleatum, where T‐cell and NKT‐cell responses to these bacteria in patients with periodontitis grade B or C are not fully elucidated. The objective is to determine if exaggerated proinflammatory Th‐cell responses to periodontitis‐associated bacteria, but not commensal bacteria, is a characteristic of increased periodontitis grade.MethodsMononuclear cells from patients with periodontitis grade C (n = 26) or grade B (n = 33) and healthy controls (HCs; n = 26) were stimulated with P. gingivalis, F. nucleatum or the commensal bacteria, Staphylococcus epidermidis and Cutibacterium acnes. Cytokine production by different T‐cell populations and FOXP3‐expression by regulatory T cells were assessed by flow cytometry.ResultsCompared to HCs, grade C patients had decreased frequencies of interleukin (IL)‐10‐producing CD4+ T cells before stimulation (p = .02) and increased frequencies of IFN‐y‐producing CD4+ T cells after stimulation with P. gingivalis (p = .0019). Grade B patients had decreased frequencies of FOXP3+ CD4+ T cells before (p = .030) before and after stimulation with anti‐CD2/anti‐CD3/anti‐CD28‐loaded beads (p = .047), P. gingivalis (p = .013) and S. epidermidis (p = .018). Clinical attachment loss correlated with the frequencies of IFN‐y‐producing Th1 cells in P. gingivalis‐ and F. nucleatum‐stimulated cultures in grade B patients (p = .023 and p = .048, respectively) and with the frequencies of Th17 cells in P. gingivalis‐stimulated cultures (p = .0062) in grade C patients. Patients with periodontitis grade C or grade B showed lower frequencies of IL‐10‐producing NKT cells than HCs in unstimulated cultures (p = .0043 and p = .027 respectively).ConclusionsBoth periodontitis groups showed decreased frequencies of immunoregulatory T‐cell and NKT cell subsets at baseline. Clinical attachment loss correlated with P. gingivalis‐induced Th17‐responses in grade C patients and with Th1‐responses in grade B patients when cells were stimulated with P. gingivalis, supporting that dysregulated pro‐inflammatory T‐cell responses to periodontitis‐associated bacteria contribute to the pathogenesis of periodontitis.