Depressed responsiveness of peripheral blood mononuclear cells to heat-shock proteins in periodontitis patients.

The extensive homology between human and bacterial heat shock proteins (HSPs) may play a role in autoimmune reactions in periodontitis. Thus, we questioned whether peripheral blood mononuclear cell (PBMC) proliferative responses to HSPs are different between periodontitis patients and control subjects with gingivitis. The proliferative responses of PBMCs of patients (n = 10) and controls (n = 12) to recombinant mycobacterial HSP60 (MycHSP60) and HSP70 (MycHSP70), as well as recombinant human HSP60 (HumHSP60) and HSP70 (HumHSP70), were investigated. In addition, the proliferative responses to Candida albicans and purified protein derivatives of Mycobacterium (PPD) were included. Mean responses to HumHSP60, MycHSP60, and HumHSP70 were significantly lower for patients compared with controls. The responses to MycHSP70 showed a similar trend. However, when Candida and PPD were used as antigens, there was no difference in responses of the PBMCs between the periodontitis patients and controls. The level of IFN-gamma in the supernatants of the cells stimulated with HSPs was lower in the patients compared with controls. This concurs with the current hypothesis that periodontitis patients have a depressed Th1 response. Furthermore, we found that with an increasing estimated subgingival bacterial load, periodontitis patients mount a decreasing immune response to HSPs, while the controls showed a positive correlation between these two parameters. From these findings, we speculate that poor reactivity to HSPs may be a susceptibility factor for destructive periodontal disease and may need to be considered in the pathogenesis of this condition.

The stimulation of human peripheral blood lymphocytes by solubilized dental plaque: macrophage and T-cell dependence.

This study compared the ability of human peripheral blood lymphocyte subpopulations from individuals with moderate periodontitis to proliferate in response to stimulation with solubilized dental plaque, phytohemagglutinin (PHA), pokeweed mitogen (PWM) and purified protein derivative (PPD). Unseparated mononuclear lymphocytes and recombined purified T and B lymphocytes (4/1) responded significantly to all of the stimulants. DNA synthesis in response to solubilized dental plaque was maximal after 6 to 7 days of culture; the optimum dose was usually 10 to 20 micrograms/ml. T lymphocyte subpopulations purified by rosetting with sheep red blood cells and density gradient centrifugation responded well to PHA and PWM, but were unresponsive to solubilized dental plaque and PPD unless supplemented with 2% autologous macrophages, demonstrating that T cell responses to solubilized dental plaque and to PPD are macrophage-dependent. T cell-depleted enriched B lymphocyte subpopulations were poorly responsive to all of the tested stimulants; however, the responses of these cells to solubilized dental plaque and to the known T cell-dependent B cell mitogens PWM and PPD were increased significantly by the presence of 10% mitomycin C-treated T cells, demonstrating that B cell proliferation to solubilized dental plaque is T cell-dependent. Thus, cellular interactions between macrophages, T lymphocytes and B lymphocytes are required to obtain optimal proliferative lymphocyte responses to solubilized dental plaque. Since both T and B lymphocytes respond to dental plaque stimulants, they both have the potential to mediate periodontal inflammation and tissue destruction whenever dental plaque stimulants gain entrance into the periodontal tissues.

Depletion of alveolar macrophages exerts protective effects in pulmonary tuberculosis in mice.

Mycobacterium tuberculosis bacilli are intracellular organisms that reside in phagosomes of alveolar macrophages (AMs). To determine the in vivo role of AM depletion in host defense against M. tuberculosis infection, mice with pulmonary tuberculosis induced by intranasal administration of virulent M. tuberculosis were treated intranasally with either liposome-encapsulated dichloromethylene diphosphonate (AM(-) mice), liposomes, or saline (AM(+) mice). AM(-) mice were completely protected against lethality, which was associated with a reduced outgrowth of mycobacteria in lungs and liver, and a polarized production of type 1 cytokines in lung tissue, and by splenocytes stimulated ex vivo. AM(-) mice displayed deficient granuloma formation, but were more capable of attraction and activation of T cells into the lung and had increased numbers of pulmonary polymorphonuclear cells. These data demonstrate that depletion of AMs is protective during pulmonary tuberculosis.

The immunotoxicity of triphenyltin chloride in mice.

The immunotoxicity of triphenyltin chloride (TPTC) in mice was investigated. 1) When TPTC was injected intraperitoneally (i.p.) into mice at doses between 1 and 10 mg/kg for 14 d, a reduction in the weights of thymus and spleen was noticed, however, the body weight was not changed significantly. 2) The production of hemolytic plaque forming cells in the spleen of mice immunized with sheep red blood cells (SRBC) was inhibited by the administration of 10 mg/kg of TPTC. 3) The i.p. injection of TPTC at a dose of 10 mg/kg for 5 d after the primary immunization of mice with dinitrophenylated ascaris antigen resulted in suppression of immunoglobulin E antibody formation in primary immune response, but did not affect the secondary immune response. 4) The production of antibody against polyvinylpyrrolidone (T cell independent antigen) was not affected by the administration of TPTC. 5) The production of effector T cells which are able to cause SRBC- or tuberculin-induced footpad reaction in mice and the induction of cytotoxic T cell in local graft versus host reaction in mice were also inhibited by TPTC. These results indicate that TPTC inhibits both the T cell dependent humoral and cellular immune responses in mice.

Systemic Th1/Th2 cytokine responses to paternal and vaccination antigens in preeclampsia: no differences compared with normal pregnancy.

PROBLEM: A Th1-shift has been suggested to be involved in the pathogenesis of preeclampsia. This study was designed to compare Th1/Th2 related cytokine secretion in blood between women with preeclampsia (n = 15) and normal pregnancies (n = 15), using a high-sensitivity technique for cytokine detection. METHODS OF STUDY: Spontaneous as well as 'fetus-specific' and recall antigen-specific (purified protein derivate of Mycobacterium tuberculosis, tetanus toxoid and lipopolysaccharide) secretion of interferon-gamma, interleukin (IL)-4, IL-10 and IL-12 in peripheral blood mononuclear cells (PBMC) was detected by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT). Fetus-specific secretion was induced by stimulation with paternal PBMC in a mixed leukocyte culture assay. RESULTS: All cytokines were secreted by PBMCs both from women with preeclampsia and women with normal pregnancies. No differences in the number of cytokine-secreting cells were found between the two groups. CONCLUSIONS: No evidence was found for a shift in the systemic Th1/Th2 responses, in preeclampsia compared with normal pregnancy. This does, however, not exclude differences in the local immune responses related to the fetoplacental unit.