Comparative analysis of immune cell subsets in peripheral blood from patients with periodontal disease and healthy controls

Abstract

Periodontitis is a chronic inflammatory disease caused by the colonization of teeth by the bacterial plaque biofilm and the resultant host immune responses in adjacent periodontal tissues. Disease severity can vary dramatically between patients with periodontitis, with some subjects displaying inflammation without bony destruction (gingivitis), while others experience chronic progressive or rapidly aggressive gingival connective tissue damage and bone loss. To determine whether peripheral immune dysregulation is associated with periodontitis, we performed extensive analysis of immune cell subsets in peripheral blood from patients with chronic or aggressive periodontitis versus periodontally healthy control subjects. Peripheral blood mononuclear cells (PBMC) from patients with chronic periodontitis or aggressive periodontitis and from periodontally healthy controls were analysed by 8-10-colour flow cytometry for the frequencies of various lymphocyte subsets, including interleukin (IL)-17-, interferon (IFN)-γ-, tumour necrosis factor (TNF)-α- and IL-10-producing cells, and the frequencies and phenotype of monocytes. Cytokine levels in serum from the different groups were determined by Luminex assay. We found no significant differences in the frequencies of major immune cell populations [CD4 T cells, CD8 T cells, γδ T cells, CD4 CD45RO CD25 CD127 regulatory T cells (T ), CD19 B cells, CD14 monocytes] or of cytokine-producing T cells, or in the phenotype of CD14 monocytes in peripheral blood from these patient cohorts. Additionally, no significant differences were observed in serum levels of prototypical inflammatory cytokines. These results suggest that the local gingival inflammatory response is not reflected by obvious changes in major blood immune cell subset frequencies.

Peripheral T helper cell profiles during management of periodontitis

“…IFN-γ + cells were significantly lower at baseline, and 3-and 6-months post-treatment compared to health which is contrary to several studies in peripheral blood that reported higher CD4 + IFN-γ + cells in periodontitis compared to health (Chen et al, 2016;Schmidt et al, 2014) or reported no significant differences (Cheng et al, 2018;Lima et al, 2011;Okada et al, 2017). Fewer IFN-γ + expressing cells at baseline were mirrored by lower IFN-γ production upon stimulation with P. gingivalis.…”

“…Thus, the healthy control group in this study includes health and localized gingivitis cases and the results should be interpreted in light of this (Cheng et al, 2018).…”

“…Altogether, there is a consensus that local microbial dysbiosis and ensuing immune response in periodontitis may have distant systemic effects (Chapple & Genco, 2013; Tonetti & Van Dyke, 2013). Previous literature investigating Th cells in peripheral blood mononuclear cells (PBMCs) is conflicting with studies reporting higher Th1 (Chen et al, 2016; Schmidt et al, 2014), Th2 (Aoyagi et al, 1995; Lima et al, 2011), Th17 (Chen et al, 2016; Luo et al, 2014; Schmidt et al, 2014) and Treg (Sabarish et al, 2016) cells in periodontitis or no significant differences (Cheng et al, 2018; Gemmell & Seymour, 1998; Lalla et al, 2007; Okada et al, 2017) or treatment‐related reduction (Zhao et al, 2011). Therefore, this study aimed to investigate the longitudinal variation of IFN‐γ + , IL‐4 + , IL‐17 + and Foxp3 + cells and their double‐positive expression in CD4 + and TCRαβ + cells in PBMCs during management of periodontitis up to 12‐months post‐treatment.…”

Peripheral memory T‐cell profile is modified in patients undergoing periodontal management

“…Memory T‐cell profiles in peripheral blood in response to therapy are not well established in periodontitis. Previously, CD4 + CD45RA + naïve (Afar et al, 1992) and CD4 + CD45RO + antigen‐experienced memory cells (Afar et al, 1992; Aoyagi et al, 1995) were reported to be higher in periodontitis, whereas others reported that neither CD4 + CD45RA + naïve (Seymour et al, 1997) nor CD4 + CD45RO + memory cells (Cheng et al, 2018) were significantly different in chronic or aggressive periodontitis compared to health. Longitudinal studies have reported significantly increased CD4 + CD45RA + naïve cells post‐treatment (Kimura et al, 1991).…”

TLR3 activation modulates immunomodulatory properties of human periodontal ligament cells

“…IFN levels are increased in the gingival crevicular fluid 10,11 and saliva 12 from periodontitis patients. 13 IFN activation of stem cells from periodontal ligament, umbilical cord, and adipose tissue showed an immunosuppressive response by inhibiting proliferation of peripheral blood mononuclear cells (PBMCs). 14 Interestingly, the response of these cells appeared to depend on the presence of members of toll-like receptors (TLRs).…”