Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection
Yen-Tung A. Teng, … , Richard P. Ellen, Josef M. Penninger
Yen-Tung A. Teng, … , Richard P. Ellen, Josef M. Penninger
Published September 15, 2000
Citation Information: J Clin Invest. 2000;106(6):R59-R67. https://doi.org/10.1172/JCI10763.
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Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection

Abstract

Periodontitis, a prime cause of tooth loss in humans, is implicated in the increased risk of systemic diseases such as heart failure, stroke, and bacterial pneumonia. The mechanisms by which periodontitis and antibacterial immunity lead to alveolar bone and tooth loss are poorly understood. To study the human immune response to specific periodontal infections, we transplanted human peripheral blood lymphocytes (HuPBLs) from periodontitis patients into NOD/SCID mice. Oral challenge of HuPBL-NOD/SCID mice with Actinobacillus actinomycetemcomitans, a well-known Gram-negative anaerobic microorganism that causes human periodontitis, activates human CD4+ T cells in the periodontium and triggers local alveolar bone destruction. Human CD4+ T cells, but not CD8+ T cells or B cells, are identified as essential mediators of alveolar bone destruction. Stimulation of CD4+ T cells by A. actinomycetemcomitans induces production of osteoprotegerin ligand (OPG-L), a key modulator of osteoclastogenesis and osteoclast activation. In vivo inhibition of OPG-L function with the decoy receptor OPG diminishes alveolar bone destruction and reduces the number of periodontal osteoclasts after microbial challenge. These data imply that the molecular explanation for alveolar bone destruction observed in periodontal infections is mediated by microorganism-triggered induction of OPG-L expression on CD4+ T cells and the consequent activation of osteoclasts. Inhibition of OPG-L may thus have therapeutic value to prevent alveolar bone and/or tooth loss in human periodontitis.

Authors

Yen-Tung A. Teng, Hai Nguyen, Xuijuan Gao, Young-Yun Kong, Reginald M. Gorczynski, Bhagirath Singh, Richard P. Ellen, Josef M. Penninger

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Figure 2

Regulation of alveolar bone destruction by A. actinomycetemcomitans–reactive CD4+ T cells.

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Regulation of alveolar bone destruction by A. actin...
Groups of mice as indicated were either left untreated or inoculated with A. actinomycetemcomitans. CD4+ T, CD8+ T, or B cells were depleted from mice using specific Ab’s and human complement as described in Methods. Data shown are the relative amounts (± SD) of alveolar bone loss accumulated by the end of 8 weeks, expressed as a percentage of the bone loss in the positive control, Aa-infected BALB/c mice (100%). Group I, sham-infected, nondepleted NOD/SCID mice (n = 10); group II, Aa-infected, nondepleted HuPBL-NOD/SCID mice (n = 32); group III, Aa-infected, CD4+ T cell–depleted NOD/SCID mice (n = 20); group IV, sham-infected, CD4+ T cell–depleted NOD/SCID mice (n = 9); group V, Aa-infected, CD8+ T cell–depleted NOD/SCID mice (n = 12); group VI, Aa-infected, B cell–depleted NOD/SCID mice (n = 16); group VII, Aa-infected NOD/SCID mice bearing adoptively transferred Aa-reactive CD4+ T cells (AT-CD4T) plus irradiated autologous monocytes/macrophages as APCs (n = 10); group VIII, Aa-infected NOD/SCID mice bearing adoptively transferred irradiated autologous monocytes/macrophages as APCs (irr-APC; n = 6). AStatistically significant difference in bone loss between group III and groups II, IV, V, and VI (P < 0.005).