Cells In Periodontitis Research Articles

Aspects of adaptive host response in periodontitis

To review host response in periodontitis with respect to cellular composition of lesions, T cell receptor (TCR) gene expression, cytokine profiles of T-helper (Th) cells and autoimmune components. The studies included were confined to human material (biopsies, gingival crevicular fluid, blood from subjects with periodontitis). In periodontitis lesions, plasma cells are the most common cell type and represent about 50% of all cells, while B cells comprise about 18%. The proportion of B cells is larger than that of T cells and Th cells occur in larger numbers than T cytotoxic cells. Polymorphonuclear cells and macrophages are found in fractions of less than 5% of all cells. Lesions in aggressive and chronic forms of periodontitis exhibit similar cellular composition. Differences in disease severity, however, may reflect increases in plasma cell and B cell densities. B cells serve as important antigen-presenting cells in periodontitis. The periodontitis lesion expresses a unique TCR gene repertoire that is different from that in blood. The role of superantigens in periodontitis is unclear. There are few studies using comparative designs and unbiased quantitative methods regarding Th-1 and Th-2 cells in periodontitis. The relative dominance of B cells and plasma cells in periodontitis lesions cannot entirely be explained by enhanced Th-2 functions but maybe because of an imbalance between Th-1 and Th-2. Autoimmune reactions are evident in periodontitis lesions. The role of auto-antibodies in the regulation of host response in periodontitis, however, needs to be clarified. Auto-reactive B cells occur in larger proportions in subjects with periodontitis than in healthy controls.

Is periodontal disease mediated by salivary baff in sjögren's syndrome?

To correlate the periodontal status of 15 patients with primary Sjögren's syndrome (SS) with their salivary levels of BAFF. The periodontal status of 15 patients who fulfilled the criteria for primary SS was compared with that of 15 controls with xerostomia who did not fulfill the criteria for primary SS but had similar symptoms of dry mouth. The level of BAFF was measured in paired samples of saliva and serum using in-house enzyme-linked immunosorbent assays. Periodontitis was assessed by the plaque index, the modified gingival index, the papillary bleeding index, and the periodontal pocket depth. Notwithstanding the better oral hygiene practices of the patients with primary SS compared with those of the xerostomia controls and the subsequent reduction of their plaque index scores, complications of periodontitis, such as bleeding, gingival hypertrophy, and periodontal pockets, were not improved. This failure to ameliorate the complications of periodontitis in patients with primary SS was associated with high levels of BAFF in their saliva compared with the levels in xerostomia controls (7.4 +/- 2.1 versus 1.0 +/- 0.4 ng/ml [P < 0.002]). The levels of BAFF in saliva did not correlate with the levels in sera but did correlate with the periodontal pocket depth (P < 0.002). These findings are similar to the bone resorption observed in patients with rheumatoid arthritis. They suggest that the known effect of B cells in periodontitis would be partly mediated by salivary BAFF in patients with primary SS.

Antigen-presentation and the role of dendritic cells in periodontitis.

Antigen-presentation and the role of dendritic cells in periodontitis.

Upregulation of co-stimulatory molecule expression and dendritic cell marker (CD83) on B cells in periodontal disease.

T cells and their cytokines are well known for their important role in the pathogenesis of periodontitis. To date, the role of antigen presenting cells (APCs), which are known to be critical in the regulation of T cell response, has been poorly investigated in periodontitis. In this study, we analyzed the expression of co-stimulatory molecules (CD80 and CD86) and CD83, which is a marker of mature dendritic cells, on gingival cells that were isolated from severe periodontitis tissues, with the use of flow cytometry. Significant upregulation of CD86 and CD83 expression was detected in periodontitis lesions, and most of this occurred on B cells. In vitro peripheral blood mononuclear cell cultures showed that stimulation with different periodontopathic bacteria, that included Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Actinomyces viscosus, upregulated both CD86 and CD83 expression on B cells. Therefore, the presence of plaque bacteria may be responsible for the enhanced expression seen in vivo on gingival B cells. APC function by bacterial-activated B cells was further investigated using allogeneic mixed leukocyte reactions. After 24 h culture with either A. actinomycetemcomitans or P. gingivalis, these activated B cells performed as potent APCs in mixed leukocyte reactions, and they stimulated T cells to produce high levels of gamma interferon and minimal interleukin-5. In conclusion, periodontopathic bacterial-induced B cell activation with upregulation of CD86 and CD83 may be associated with enhanced APC function. The results of this study suggest, therefore, that infiltrated gingival B cells have a possible role as APCs in the regulation and maintenance of local T cell response in periodontitis.

Microvasculature in gingivitis and chronic periodontitis: disruption of vascular networks with protracted inflammation.

Gingivitis occurring when bacterial plaque accumulates in the gingival crevice provides a convenient and interesting model for chronic inflammation in humans. In some patients, gingivitis progresses to the destructive lesion of periodontitis, involving the formation of periodontal pockets. The basis for pocket formation and progression is not as yet clear, although neutrophilic polymorphonuclear leukocytes (PMN) appear to play a protective role. Vascular changes appear to either facilitate or inhibit PMN function with the effect of either protecting from, or stimulating, periodontitis. Contrary to most circumstances, high endothelial cells in periodontitis are involved with PMN rather than lymphocyte emigration. Expansion of the microvasculature through increased vascular diameter and tortuosity as well as the development of high endothelial cells appears to protect from periodontitis by increasing the supply of both plasma defense factors and PMN to the tissues. Vascular changes that may oppose this and promote periodontitis are the formation of perivascular hyaline material and accumulation of basement membrane rests. The inadequate tissue turnover that accumulation of these vascular products represents can be argued as a vascular response to a chronic inflammation that has failed to eliminate the irritant. It is suggested that these vascular changes may account for the highly localized and burst-like pattern of pocket formation in periodontitis. Finally, it is possible that the recent observation that periodontitis is an independent risk factor for systemic vascular disease may reflect stimulation of acute phase protein synthesis by cytokines released by periodontal high endothelial cells.

Phenotypical and functional analysis of T cells in periodontitis.

To explore aspects of cellular immune responses in the pathogenesis of periodontitis we analyzed phenotype and function of peripheral T cells. Two groups of subjects participated: one group consisted of 10 highly susceptible patients with severe periodontitis (mean age 29 years) and a control group consisted of 10 age, gender and race matched subjects with gingivitis. From all subjects peripheral blood was collected. The results showed that the numbers of CD3+, CD4+ and CD8+ T cells as well as the CD4/CD8 ratio, and the proliferative capacity of T cells, were not different between the two groups of subjects. Also, proportions of naive and memory T cells for both the CD4+ and CD8+ subpopulations were not different. Functional heterogeneity within the CD4+ and CD8+ T cell compartments was determined by intracellular analysis of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production. On the basis of these latter analyses among CD4+ and CD8+ cells, T helper (Th) 1 or Th2 function and T cytotoxic (Tc) 1 or Tc2 function, respectively, could be deduced. No significant differences in proportions of CD4+ and CD8+ T cells positive for intracellular IFN-gamma or IL-4 were observed between periodontitis patients and gingivitis controls; however a higher level of intracellular IL-4 in CD8+ T cells was seen in periodontitis patients. This might indicate that there is a shift towards a Tc2 function within the CD8+ T cell subpopulation. The current explorative study suggests that further research into the role of CD8+ T cells in the pathogenesis of periodontitis is warranted.

Elevated Proportion of Natural Killer T Cells in Periodontitis Lesions: A Common Feature of Chronic Inflammatory Diseases

Although periodontitis is a chronic inflammatory disease caused by a group of so-called periodontopathic bacteria, autoimmune mechanisms have also been implicated in the disease process. Recently, a unique subset of lymphocytes designated natural killer (NK) T cells expressing the Valpha24JalphaQ invariant T cell receptor (TCR) has been reported to have a regulatory role in certain autoimmune diseases. Therefore, we investigated the proportion of the invariant Valpha24JalphaQ TCR within the Valpha24 T cell population in periodontitis lesions and gingivitis lesions using single-strand conformation polymorphism methodology. NK T cells were identified with a specific JalphaQ probe whereas the total Valpha24 TCR was identified using an internal Calpha probe. NK T cells were a significant proportion of the total Valpha24 population both in periodontitis lesions and to a lesser extent in gingivitis lesions but not in the peripheral blood of either periodontitis patients or nondiseased controls. Using immunohistochemistry, some of Valpha24(+) cells in the periodontitis lesions seemed to associate with CD1d(+) cells, which are specific antigen-presenting cells for NK T cells. Although the mechanism underlying the elevation of NK T cells in periodontitis and in gingivitis lesions remains unclear, it can be postulated that NK T cells are recruited to a play regulatory role in the immune response to bacterial infection.

Requirement of B7 costimulation for Th1-mediated inflammatory bone resorption in experimental periodontal disease.

The CD28 costimulation at TCR signaling plays a pivotal role in the regulation of the T cell response. To elucidate the role of T cells in periodontal disease, a system of cell transfer with TCR/CD28-dependent Th1 or Th2 clones was developed in rats. Gingival injection of specific Ag, Actinobacillus actinomycetemcomitans 29-kDa outer membrane protein, and LPS could induce local bone resorption 10 days after the transfer of Ag-specific Th1 clone cells, but not after transfer of Th2 clone cells. Interestingly, the presence of LPS was required not only for the induction of bone resorption but also for Ag-specific IgG2a production. LPS injection elicited the induction of expression of both B7-1 and B7-2 expression on gingival macrophages, which otherwise expressed only MHC class II when animals were injected with Ag alone. The expression of B7 molecules was observed for up to 3 days, which corresponded to the duration of retention of T clone cells in gingival tissues. Either local or systemic administration of CTLA4Ig, a functional antagonist of CD28 binding to B7, could abrogate the bone resorption induced by Th1 clone cells combined with gingival challenge with both Ag and LPS. These results suggest that local Ag-specific activation of Th1-type T cells by B7 costimulation appeared to trigger inflammatory bone resorption, whereas inhibition of B7 expression by CTLA4Ig might be a therapeutic approach for intervention with inflammatory bone resorption.

Paradoxical role of PGE2and cAMP in Actinobacillus actinomycetem-comitants strain Y4-induced lymphocyte proliferation

An immune mechanism has been suggested in the pathogenesis of periodontal disease. Actinobacillus actinomycetemcomitants (Aa) has been implicated as one of the etiological agents that induces the major immune response together with a dense infliltrate of inflammatory cells. But the exact role of these immune cells in periodontal disease has not yet been clarified. In this study the T lymphocyte (TL) proliferative response was evaluated after having being exposed to free cell supernatant (SN) from Aa. Aa SN increased TL proliferation. This mitogenic effect of Aa SN was attenuated by pretreating TL with indomethacin (INDO) or acetylsalicilyc acid (ASA) but not by polymyxin B. The inhibitory effect of INDO on cell proliferation was reversed by the addition of prostaglandin E2(PGE2) to the culture assay. Moreover, when immune cells were exposed to Aa SN they were able to generate PGE2at the same time as intracellular levels of cAMP decreased. Both, PGE2release and decrease accumulation of cAMP in TL were blunted by treated lymphocytes with INDO. In this paper we demonstrate that cell free SN from Aa induces a mitogenic effect on murine lymphocytes. The mechanism involves the host's immunecompetent cells and the release of PGE2and appears not to be induced by capsular-like polysaccharide antigen. Results show a paradoxical mitogenic effect of Aa SN accompanied by increased generation of PGE2and decreased production of cAMP by lymphocytes.

A Histological Analysis of T and B Cells in Periodontal Tissue Destruction

We immunohistologically examined the cell densities and distribution of T and B cells in periodontitis and analyzed their relationship in terms of periodontal tissue destruction. Specimens were labeled with monoclonal antibodies for T cells (CD3) and B cells (CD20) and developed using the double staining technique. CD3+ cells appeared in low density infiltrates and increased gradually with the number of total infiltrates; in contrast, CD20+ cells did not appear in small infiltrates but increased rapidly with the number of infiltrates. The number of fibroblastic cells negatively correlated with that of the total infiltrates and CD20+ cells, but it did not correlate with the number of CD3+ cells. These findings suggest that the T cells infiltrated into the inflamed sites at the onset and increased gradually with the development of inflammation and that B cells infiltrated later than T cells and their number increased rapidly with inflammation.

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Interleukin-6 (IL-6) is involved in the final differentiation of B cells into antibody-producing cells. Recent studies reveal that IL-6 plays an important role in inflammation. Histopathological studies showed that a large number of plasma cells in periodontitis is usually seen in the apical parts of cellular infiltrates beneath the periodontal connective tissues. This evidence suggests that IL-6 may play a critical role in the development of periodontitis. Therefore, we examined IL-6 production in the gingival tissues. Twelve periodontitis patients and five gingivitis patients were included in this study. Nine individuals with healthy periodontium acted as control subjects. Biopsy specimens were dissected into fragments 3 mm in diameter and plated onto 24-well culture plates with RPMI 1640 medium. IL-6 activity in the culture supernatants was measured by IgM production assay using the cell line SKW6-CL4. IL-6 activity was detected at significantly higher levels (P less than 0.001) in culture supernatants from the gingival tissues in periodontitis (23.2 +/- 14.4 units/ml) and gingivititis (12.5 +/- 3.4 units/ml) than in control tissues (2.3 +/- 1.2 units/ml). Subsequently, the relationship between IL-6 activity and clinical stages was examined. The IL-6 levels before initial preparation (23.2 +/- 14.4 units/ml) were significantly higher (P less than 0.001) than those after initial preparation (1.4 +/- 1.8 units/ml), but were not associated with either periodontal pocket depth or the extent of alveolar bone resorption in periodontitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Helper and suppressor T cells in periodontal disease.

The ratio of helper (T4+) to suppressor (T8+) T cells was determined in a population of periodontitis patients and in normal subjects. Although patients as a group were found to have the same T4/T8 ratio as normal individuals, that subgroup of patients previously identified as T cell low responders to oral microorganisms exhibited a relative increase in circulating suppressor T cells. Conversely, unusually low T4/T8 ratios were predictive of low level T cell proliferative responses generated against 7/12 oral microorganisms tested. Patients with low T4/T8 ratios had significantly more redness and bleeding on probing than did those with high T4/T8 ratios, but did not differ with respect to plaque, pocket depth, attachment loss, or episodes of disease activity. These results extend previous observations concerning the relationship between the in vitro T cell response to oral microorganisms and gingival inflammation.

Chemotactic activity in periodontal disease

Extracts of gingival tissue obtained from periodontal patients, but not from patients with clinically jealthu tissue, were found to be chemotactic for human mononuclear cells. The chemotactic activity of the extracts could be suppressed by anti‐C5 serum. The data obtained suggest that C5‐related compound are major factors in the chemotaxis of mono nuclear cells in periodontal disease.

Immunoglobulin bearing lymphocytes and plasma cells in human periodontal disease.

Gingival biopsies from areas characterized as clinically normal, mild gingivitis, or periodontitis were examined. Immunoglobulin (IgG, IgA, IgM, IgE and IgD) bearing cells at the sulcular and oral epithelium ‐ lamina propria junctions as well as the central lamina propria areas were quantitated. Normal gingiva (P. I. = 0‐0·2) contained few lymphocytes and plasma cells. Biopsies from areas of mild gingivitis (P. I. = 0·2‐1) were infiltrated at the sulcular epithelium ‐ lamina propria junction by lymphocytes lacking membrane associated immunoglobulins (94 %). Few plasma cells were evident. In contrast, tissue associated with periodontitis (P. I. = 4·0–8·0) contained significant numbers of immunoglobulin bearing lymphocytes (78 %, IgG; 9 %, IgM; and 4 % IgA) and plasma cells (67 %, IgG; 24 %, IgM; and 8 % IgA) distributed throughout all three major tissue areas.These findings indicated that the nature of cellular infiltrates differed in mild gingivitis and periodontitis. The presence of predominantly IgG and IgM containing cells in periodontitis had important implications for the contribution of nonspecific effector mechanisms to the destruction of periodontal tissue.

The fine structure of human connective tissue mast cells in periodontal disease.

Electron microscopic examination of the walls of periodontal pockets revealed that connective tissue mast cells were distributed throughout the tissue. These cells had a variety of shapes, and were often in close association with remaining collagen fibers, as well as with smaller fibrils and other collagen fragments. Totally distrupted, necrotic mast cells were also observed which had morphologically intact granules in continuity with the extracellular space.

The fine structure of human epithelial mast cells in periodontal disease.

Ultrastructural study of the lining of the pathologic pockets of patients with chronic periodontal disease revealed the presence of mast cells within the epithelial layer. These intraepithelial mast cells had a variety of unusual shapes, and frequently appeared dendritic. These cells also had cytologic features which suggested that they were actively synthesizing mast cell granules and releasing them into the extracellular space. The findings indicate that intraepithelial mast cells may play a role in the pathogenesis of the sulcular epithelial changes which are seen in human periodontal disease.