Involvement of T-Lymphocytes in Periodontal Disease and in Direct and Indirect Induction of Bone Resorption

Abstract

Periodontal disease is a peripheral infection involving species of Gram-negative organisms. T-lymphocytes can be found in the dense inflammatory infiltrate in this disease. CD4+ and CD8+ T-cells are present in periodontal lesions, as are memory/activated T-lymphocytes. In addition, Th I -and Th2-type T-lymphocytes and their associated cytokines with a subtle polarization to Th 1 may be present. Th 1-type T-cells up-regulate the production of pro-inflammatory cytokines IL-1 and TNF-cx, which can induce bone resorption indirectly by promoting differentiation of osteoclast precursors and subsequently by activating osteoclasts. Such osteoclast differentiation is dependent on stimulation of osteoprotegerin ligand (OPG-L) production by osteoblastic cells. By contrast, activated T-cells, by virtue of direct production and expression of OPG-L, can directly promote osteoclast differentiation. OPG-L appears to be predominantly expressed on Th I -type cells. The direct and indirect T-cell involvement in periodontal bone resorption appears to be dependent on the degree of Th 1-type T-cell recruitment into inflamed gingival tissues. This T-cell recruitment is regulated by adhesion molecules and chemokines/chemokine receptors. The adhesion molecules involved include cx4 and cx6 integrins, LFA-1, and ICAM-1. The Th I -type T-cells preferentially express CCR5 and CXCR3, which are found prominently in diseased gingivae. By contrast, little CCR4, expressed by Th2-type T-cells, can be detected. Also, the chemokine ligands RANTES, MIPl-cx (both CCR5), and IP-10 (CXCR3 ligand) were elevated in inflamed periodontal tissues. The T-cell features in diseased periodontal tissues can be compared with those in rheumatoid arthritis, wherein bone resorption often attributed to Thl-type T-cell involvement has also been demonstrated.

Tight-adherence genes of Actinobacillus actinomycetemcomitans are required for virulence in a rat model

“…However, it is known that A. actinomycetemcomitans can cause bone loss directly by means of bacterial enzymes (47,52) and toxins such as lipopolysaccharide (53), or indirectly by stimulation of host response mediators (40). Recent evidence suggests that A. actinomycetemcomitanssensitized T cells can result in expression of RANK-L (receptor activator of NF-B ligand) by activated T helper 1 cells, which in turn can induce osteoclastogenesis, osteoclast activation, and bone loss (54). This mechanism of bone loss is compelling because it has been described in a rat model.…”

Endogenous IL-15 Sustains Recruitment of IL-2Rβ and Common γ and IL-2-Mediated Chemokine Production in Normal and Inflamed Human Gingival Fibroblasts

“…Periodontal disease is caused by infection with anaerobic Gramnegative organisms such as Porphyromonas gingivalis, and T and B cells as well as neutrophils are found in the dense inflammatory infiltrate in this disease (16,17). In addition, Th1-or Th2-type T cells and their associated cytokines contribute to the onset and healing of this disease (27). IL-2 is secreted from activated T cells and is a key cytokine in both Th1 and Th2 responses (34).…”

“…Periodontal disease is clinically identified as an inflammation of periodontal tissues caused by Gram-negative organisms, and is characterized by the infiltration of T and B cells as well as neutrophils into inflamed gingival tissues, resulting in direct and indirect destruction of periodontal tissue (27). The T cell features in diseased periodontal tissues can be compared with those in rheumatoid arthritis.…”

Porphyromonas gingivalis Induces RANKL in T-cells

“…It is now well established that T-cells, have a key role in the pathogenesis of periodontal disease, particularly by mediating the resorption of the alveolar bone [8,9]. The notion that CD4+ Th1 cells are central to the cell-mediated immunity events associated with the disease, particularly through interferon-γ production, is now challenged by the discovery of the interleukin-17-producing Th17 population [10].…”