Evidence of mitogenic activity in periodontitis-associated bacteria

Abstract

This study examines several periodontitis-associated bacterial isolates for the presence of mitogenic activity, as indicated by their capacity to stimulate unsensitized lymphocytes to undergo blastogenesis. Germfree mouse spleen cells responded vigorously to all of the bacterial sonic extracts tested. The kinetics and dose responses to these activators in germfree mouse spleen cell cultures paralleled those seen with the standard murine B-cell mitogen, Escherichia coli lipopolysaccharide. In contrast, Streptokinase-Streptodornase (Varidase; Lederle Laboratories) antigen elicited no response. Human cord blood lymphocytes also responded upon stimulation with these same bacterial isolates but failed to respond to Streptokinase-Streptodornase. The frequency, magnitude, and kinetics of these cord blood lymphocyte responses were remarkably similar to those seen with adult peripheral blood lymphocytes. However, in this and previous studies, individuals with unresponsive peripheral blood lymphocytes have been observed. Studies were initiated to determine whether these unresponsive leukocyte preparations truly lacked the capacity to respond to these bacteria or whether unresponsiveness reflected the presence of a regulatory cell population in these cultures. After the removal of the adherent cells from unresponsive peripheral blood lymphocyte cultures, the nonadherent cells were found to be responsive. Therefore, peripheral blood lymphocyte responsiveness appears to be regulated via an adherent cell population. The removal of adherent cells from unresponsive cord blood lymphocyte preparations resulted in a less consistent alteration to responsiveness. However, cord blood lymphocyte preparations unresponsive at a standard cell density were shown to be responsive at altered cell densities.

Activation of rat B lymphocytes by Actinobacillus actinomycetemcomitans

“…Although the data in this study implicate the B cell as the primary mitogenic responding cell type in this rat model, we can not rule out possibilities for T-cell responsiveness in human systems or for an important regulatory role for T cells (35) in the B-cell response in both murine and human systems (5). The kinetics of the murine and human systems appear to differ in vitro since human cord blood lymphocytes respond at 6 days after stimulation with A. actinomycetemcomitans sonicate (6). Although in some respects the data obtained herein confirm the demonstration of mitogenesis of human cells by A. actinomycetemcomitans sonicates (6), the use of whole cells is clearly a unique procedure.…”

“…Recently, A. actinomycetemcomitans extr. ct was found to stimulate polyclonal antibody responses and mitogenic responses in cultures of normal human peripheral blood lymphocytes (3,6). A preliminary investigation suggested that heat-killed A. actinomycetemcomitans and lipopolysaccharide of the bacterium have a potential mitogenic activity for mouse B lymphocytes (P. Chen, B. C. Nair, and R. J. Genco, J. Dent.…”

Solubilized dental plaque is mitogenic for nylon wool‐purified human cord blood T lymphocytes

“…These results indicate that soiubilized dental plaque contains one or more mitogen(s) for human T lymphocytes. The small percentage of cultures unresponsive to soiubilized dental plaque may have been due to the use of the wrong cell culture density (Donaldson et al 1983), but could also be due to undetected technical problems or the long 7-d culture times, because many of the unresponsive cultures were also unresponsive to PHA. It could be argued that a peak response in DNA synthesis after 6 to 7 d of culture by human cord blood lymphocytes sfimulated with soiubilized dental plaque resembles an antigenic response more than a mitogenic one.…”

“…Page (1982) has pointed out that cord blood contains higher levels of suppressor cells than adult peripheral blood, and has suggested that the presence of suppressor cells rather than a lack of antigenic sensitization may explain the unresponsiveness of cord lymphocytes to oral bacterial stimulants. This possibihty has received further support from Donaldson, Ranney & Tew (1983) who reported that unresponsive cord blood lymphocytes could be made to respond to oral bacteria by altering the density of the lymphocyte cultures, and attributed the unresponsiveness to the presence of adherent regulatory cells in the cord blood lymphocyte preparations. In view of these results, the present study has carried out a thorough re-examination of whether cord blood lymphocytes respond significantly to oral bacterial stimulants.…”

Polyclonal B‐cell activation in periodontitis*

“…The usual concentration of macrophages found in peripheral blood is inhibitory to stimulation by many plaque bacteria (112,116,126), If the macrophage concentration in peripheral blood lymphocytes of nonresponders is reduced, or even if the number of lymphocytes per well is changed, it is possible to get lymphocytes from all individuals to respond regardless of their periodontal condition (112), Furthermore, lymphocytes from cord blood respond very well. The average response of cord blood lymphocytes to periodontitis-associated bacteria was as high as adult responses, and in some cases was tnarkedly higher (112), In contrast, the response to a real antigen like streptokinase-streptodornase was missing in the cord blood lymphocytes, indicating lack of sensitization (112), Under appropriate conditions, the mitogens in periodontitis-associated bacteria will stimulate lymphocytes from all individuals, including lymphocytes from cord blood, V, Pathogenic potential oi PBA V,A, Association of PBA witfi disease Polyclonal B-cell activation has been associated with numerous bacterial, parasitic, viral, and autoimmune diseases (Table 4), Fvidence which supports the role of PBA in these diseases includes polyclonal hyperimmunoglobulinemia (pHIg), elevated numbers of spontaneous immunoglobuhnsecreting cells (ISC) in the blood or tissue of these patients, and autoantibody production. Infections with bacteria, parasites, and viruses often lead to detectable levels of autoantibodies including rheumatoid factor and anti-DNA anfibodies, and these may be involved in autoimmune diseases.…”