Protective and Destructive Immunity in the Periodontium: Part 2—T-cell-mediated Immunity in the Periodontium

Abstract

Based on the results of recent research in the field and Part 1 of this article (in this issue), the present paper will discuss the protective and destructive aspects of the T-cell-mediated adaptive immunity associated with the bacterial virulent factors or antigenic determinants during periodontal pathogenesis. Attention will be focused on: (i) osteoimmunology and periodontal disease; (ii) some molecular techniques developed and applied to identify critical microbial virulence factors or antigens associated with host immunity (with Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis as the model species); and (iii) summarizing the identified virulence factors/antigens associated with periodontal immunity. Thus, further understanding of the molecular mechanisms of the host's T-cell-mediated immune responses and the critical microbial antigens related to disease pathogenesis will facilitate the development of novel therapeutics or protocols for future periodontal treatments.

Interleukin-10 Inhibits Gram-Negative-Microbe-Specific Human Receptor Activator of NF-κB Ligand-Positive CD4 + -Th1-Cell- Associated Alveolar Bone Loss In Vivo

“…In summary, our data suggest an inhibitory effect of hIL-10 on RANKL ϩ -Th-cell-mediated alveolar bone loss in an experimental periodontitis model which is correlated with the effects in successfully treated periodontal tissues in AgP. The present study illustrates and confirms the important role of gram-negative-pathogen-reactive RANKL ϩ Th cells coexpressing hIFN-␥, a signature Th1 cytokine, as a critical and positive cellular determinant in complex cytokine interactions and RANKL-RANK signaling for regulating osteoclastogenesis during periodontal disease progression in vivo (called RACIN [RANKL and cytokine interactions network] [34]). Thus, further understanding of these cellular and molecular interactions under pathological conditions may facilitate the development of novel therapeutic strategies and treatment protocols when dealing with inflammatory bone disorders such as human periodontitis in the future.…”

“…The study of osteoimmunology has demonstrated that host immune responses, especially T-cell immunity, play a pivotal role in regulating osteoclastogenesis and bone remodeling (26,(32)(33)(34)(35)36). The recently identified tumor necrosis factor (TNF) family molecule receptor activator of NF-B ligand (RANKL), its receptor RANK, and its natural antagonist, osteoprotegerin (OPG), have been shown to be the key regulators of bone remodeling involved in differentiation, activation, and survival of osteoclasts and osteoclast precursors (35).…”

“…Thus, considering the complexity of APC-T-cell interactions and IL-10's effects described above, we favor the postulate that IFN-␥ up-regulates the expression of MHC-II (or -I) and other accessory molecules on APC, leukocytes, and mesenchymal cells, which may further recruit other signaling molecules and/or immune effectors associated with bone destruction (7,12,20). Alternatively, IFN-␥ may mediate its downstream effects independent of RANKL-induced osteoclastogenesis pathways under inflammatory conditions in vivo (e.g., the presence of TNF-␣ and IL-1) (26,33,34,36). Thus, the fine balance between IFN-␥ and RANKL-RANK signaling during inflammation, perhaps including the state of T-cell activation, contributes to determining the ultimate outcome of RANKL ϩ Th cells for osteoclastogenesis and bone remodeling in vivo (32-34, 36, 38).…”

Cross-Presentation by Osteoclasts Induces FoxP3 in CD8+ T Cells

“…A central observation for osteoimmunology comes from the demonstration that skeletal homeostasis is dynamically influenced by the immune system and lymphocyte-derived cytokines are among the most potent mediators of osteoclast function and osteoclastogenesis (3,(5)(6)(7)(8)(9)(10). These mediators include receptor activator of NF-B ligand (RANKL) 2 (11,12), IFN-␤ (13-15), IFN-␥ (16 -18), TNF-␣ (19 -22), IL-1␤ (23)(24)(25)(26)(27), , , IL-17 (6, 36 -38), and IL-23 (6,38).…”

Clinical applicability of natural product(s)-containing mouthwashes as adjunctive treatment of biofilm-induced gingivitis: a systematic review

“…Chronic periodontal involvement is an infectious, irreversible and destructive disease which has the contribution of the host immune system to be developed, since the production of cytokines such as interleukin-1 (IL-1), Tumor Necrosis Factor (TNF-) and prostaglandins by immune cells promotes bone resorption and destruction of conjunctive tissue by the action of osteoclasts (activated by IL-1 and TNF-) and metalloproteinases (activated by prostaglandins), respectively (Baker, 2000;Koop & Medzhitov, 2003;Teng, 2006;Alnaeeli et al, 2006).…”