No abstract

In general, the combination of periodontitis and cigarette smoking alters the parameters studied. The effects of periodontitis on CRP and IgG2 means that periodontal lesions may also leak agents, priming the peripheral neutrophils to increased CL.

SUMMARYHelicobacter pylori induces symptomatic chronic gastritis in a subpopulation of infected individuals. The mechanism(s) determining the development and severity of pathology leading to symptoms are not fully understood. In a mouse model of H. pylori infection we analysed the influence of immunoregulatory CD4 + CD25 + T cells on H. pylori colonization and gastritis. Athymic C57BL/6 nu/nu mice were reconstituted with (a) lymph node (LN) cells (b) LN cells depleted of CD25 + T cells (CD25 -LN) or (c) not reconstituted at all. Mice were then infected orally with 3 ¥ 10 8 H. pylori SS1 bacteria. At 2 and 6 weeks after the inoculation there was a significant ( P < 0·001) reduction in H. pylori colonization in athymic mice transferred with CD25 -LN cells compared to mice transferred with LN cells. Colonization was still reduced at 12 weeks after inoculation. Mice transferred with CD25 -LN cells showed an earlier onset and increased severity of gastritis as compared to mice receiving LN cells. Splenic cells isolated from mice receiving CD25 -LN cells produced the highest level of IFN-g on stimulation with H. pylori antigens in vitro, had a higher H. pylori -specific DTH response and increased infiltration of CD4 + T cells and macrophages in the gastric mucosa. Athymic mice not transferred with T cells had persistent high H. pylori colonization and displayed a normal gastric epithelium without inflammatory cells. In conclusion, CD4 + CD25 + cells reduce immunopathology in H. pylori infection, possibly by reducing the activation of IFN-g producing CD4 + T cells, even at the expense of a higher H. pylori load in the gastric mucosa.

Our findings suggest that the increased CL from peripheral neutrophils in periodontitis may be related to a constitutionally greater responsiveness of the Fcgamma-receptor.

We have earlier reported a higher Fcgamma-receptor (FcgammaR)-mediated generation of reactive oxygen species, measured as luminol-enhanced chemiluminescence (CL) from peripheral neutrophils in adult periodontitis patients. The aims of this study were to confirm our previous results and to elucidate the mechanism of this phenomenon by measuring CL in parallel with the intracellular production of hydrogen peroxide, after stimulation with opsonized bacteria. To determine whether the higher CL was associated with altered responsiveness to priming, the cells were preincubated with tumor necrosis factor alpha (TNFalpha) and lipopolysaccharide (LPS). While CL was significantly higher in subjects with periodontitis, there was no difference in hydrogen peroxide production between the patients and the controls, indicating that the hyperreactivity is related to the generation of other oxygen species than H2O2 and/or to processes in the outer cell membrane. The responsiveness to priming with LPS on CL was slightly but not significantly higher in the periodontitis group, suggesting that priming could be of value for distinguishing subjects with periodontitis. When assaying intracellular production of H2O2, TNFalpha and LPS had both a priming and an activating effect. There were no significant differences between the two groups. In conclusion, this study shows a higher FcgammaR-mediated CL of peripheral neutrophils from adult patients with periodontitis, thus confirming our earlier results. The hyperreactivity seems to be related to the outer cell membrane or to oxygen species other than H2O2.

. CT was shown to be a strong adjuvant when it was coadministered to DC with OVA and was even stronger when it was coadministered with OVA-CTB and primed for a mixed Th1-Th2 response. The antibody and T-cell responses were further enhanced if OVA was coupled to CT, implying that CT can utilize a combined carrier and adjuvant function vis-a-vis linked antigens for DC vaccination. The immunopotentiating capacity of CT-and CTB-linked antigen was associated with both upregulated secretion of interleukin-1␤ by the pulsed DC and increased expression of CD80 and CD86 on the DC surface. These results imply that CT and CTB can be used to both markedly increase and partially direct the DC vaccineinduced immune response with respect to Th1 and Th2 responses, which has obvious implications for DCbased vaccine development.Dendritic cells (DC) are professional antigen-presenting cells (APC) which act as sentinels throughout the body. Upon an encounter with an inflammatory signal, DC transport antigens to lymphoid organs, where they activate antigen-specific CD4 ϩ and CD8 ϩ T-cells and are thus one of the most important determinants of specific immune induction (2). The special ability of DC to activate naive T-cells is maturation dependent and is associated with the expression of high levels of cell surface major histocompatibility complex (MHC) molecules and costimulatory molecules, as well as the capacity to secrete chemokines that attract naive T cells. Due to the strong immunoactivating capacity of DC, administration of ex vivo antigen-pulsed DC has been shown both in animals and in humans to induce strong T-cell and B-cell responses (25,28,30,37) and to induce protection against both tumors and infectious agents (14,21,25,31,34,39).Cholera toxin (CT) and the cholera toxin B subunit (CTB) have strong immunomodulatory properties both in vivo and in vitro. Both compounds bind to GM1 ganglioside receptors present on most cells in the body, including leucocytes. CT, the cholera-inducing enterotoxin produced by Vibrio cholerae O1 and O139, is one of the most potent mucosal immunogens and adjuvants known (9,10,22,29). Full adjuvanticity requires an intact CT molecule consisting of the cell-binding pentameric B subunit noncovalently linked to the toxic ADP-ribosylating A subunit (23,29). Although CT can also modulate both specific B-cell and T-cell activation by direct actions on these cells, its primary action as an adjuvant is probably mediated through a direct effect on APC. Thus, CT has been found to directly affect both the cytokine profile and the cell surface phenotype of APC (5, 12).CTB, on the other hand, is nontoxic and a relatively inefficient adjuvant for admixed antigens, but it is a highly efficient mucosal carrier molecule for linked antigens. Chemical or genetic conjugation of some antigens to CTB can strongly enhance the induction of mucosal antibody responses to the linked antigen (8,15,20,26), but with other antigens it can give rise to immune deviation, leading to so-called antigen-specific oral tolerance per...

A single recombinant molecule, rFel d 1, is at least as sensitive for in vitro diagnostics of cat allergy as the current extract-based test. Elevated IgE antibody levels to Fel d 1 are suggested to be a risk factor for asthma in cat-allergic children.

We studied the antibody response including antibody-secreting cells (ASC) in the female genital tract of mice after mucosal immunizations with the recombinant B subunit of cholera toxin (rCTB) perorally, intraperitoneally, vaginally, and intranasally (i.n.). The strongest genital antibody responses as measured with a novel perfusion-extraction method were induced after vaginal and i.n. immunizations, and these routes also gave rise to specific immunoglobulin A (IgA) and IgG ASC in the genital mucosa. Specific ASC in the iliac lymph nodes, which drain the female genital tract, were seen only after vaginal immunization. Progesterone treatment increased the ASC response in the genital tissue after all mucosal immunizations but most markedly after vaginal immunization. We also tested rCTB as a carrier for human gamma globulin (HGG) and the effect of adding cholera toxin (CT) as an adjuvant for the induction of systemic and genital antibody responses to HGG after vaginal and i.n. immunizations. Vaginal immunizations with HGG conjugated to rCTB resulted in high levels of genital anti-HGG antibodies whether or not CT was added, while after i.n. immunization the strongest antibody response was seen with the conjugate together with CT. In summary, vaginal and i.n. immunization give rise to a specific mucosal immune response including ASC in the genital tissue, and vaginal immunization also elicits ASC in the iliac lymph nodes. We have also shown that rCTB can act as an efficient carrier for a conjugated antigen for induction of a specific antibody response in the genital tract of mice after vaginal or i.n. immunization.