Systemic treatment of anti-CD4+CD25+ T cell monoclonal antibody exacerbates sialoadenitis in submandibular glands during the early life in lupus-prone female NZB × NZWF1 mice

Background:  The maintenance mechanisms of peripheral tolerance by CD4⁺CD25⁺ T cells before the development of sialoadenitis in secondary Sjögren's syndrome (sSS) are not well understood. The aim of the present study is to examine the effect of reduction of CD4⁺CD25⁺ T cells on the development of sialoadenitis during the early life in female NZB × NZWF₁ (B/WF₁) mice, a model for human sSS.
Methods:  Female B/WF₁ mice at 3 days after birth were treated with either anti-mouse CD4⁺CD25⁺ T cells rat IgG₁ monoclonal antibody (mAb) or Rat IgG₁(control). At 25 weeks of age, autoantibodies against nucleus and cytoplasm of ductal epithelial and myoepithelial cells, and histpathology of submandibular glands were examined in the mAb-treated and control groups. Also the development of anti-Ro/SS-A antibodies was examined until 25 weeks of age in both groups.
Results:  The mAb-treated group showed severe lesions with the development of autoantibodies compared to the control group.
Conclusions:  The present results suggest that peripheral CD4⁺CD25⁺ T cells may, at least in part, contribute to down-regulate the development of sialoadenitis in submandibular glands of lupus-prone female B/WF₁ mice during their early life.     

Interleukin-1β+3953 allele 2: association with disease status in adult periodontitis

Abstract. Adult periodontitis is a complex multifactorial disease whose etiology is not well defined. The pro-inflammatory and bone resorptive properties of interleukin-1 beta (IL-1β) strongly suggest a role for this cytokine in the pathogenesis of periodontal disease. In the study reported here, the frequency of IL-1β⁺³⁹⁵³ genotypes including allele 2 of the IL-1β⁺³⁹⁵³ restriction fragment length bi-allelic polymorphism was significantly increased in patients with advanced adult periodontitis compared to those with early and moderate disease. Furthermore, allele 2 was associated with increased production of IL-1β by activated peripheral blood polymorphonuclear cells of patients with advanced disease, although this increase failed to reach statistical significance. Finally, the data obtained revealed significant linkage disequilibrium between allele 2 of the IL-1β⁺³⁹⁵³ polymorphism and allele 2 of the bi-allelic IL-1α⁻⁸⁸⁹ polymorphism in both patients and orally healthy controls. These findings provide new insight into the possible role of IL-1α and β gene polymorphisms in the susceptibility to adult periodontitis.     

The effect of FIV infection on CD4+ and CD8+ counts in periradicular lesions

AIM: The purpose of this study was to elucidate whether a decrease/increase in T-cell populations is present in the development of periradicular disease in the immunocompromised feline model. METHODOLOGY: Eight cats were immunosuppressed with steroids prior to infection with feline immunodeficiency virus (FIV). Another eight cats, age and sex matched littermates, were monitored and tested at equivalent periods of time and served as uninoculated, seronegative controls. Periradicular lesions were induced using local bacterial inoculations into the pulp of the canine teeth and assessed after one- and four-week periods, corresponding to the acute and chronic stages of the periradicular disease. Block sections were obtained and specimens were prepared for H & E and immunohistochemical staining for CD4+ and CD8+ receptors. Cells were quantified using a computer imaging system and data analysed using generalized estimating equation (GEE) regression models. RESULTS: Significantly lower CD4+ counts and CD4+/ CD8+ ratios were observed at all time periods in the periradicular region of the FIV group (P = 0.0006). No significant difference in CD8+ counts was observed between the two groups. In both groups there was a significant difference in the CD4+ counts between one week and baseline, and 1 week and 4 weeks. There was no significant difference between baseline and 4 weeks for either group. CONCLUSION: FIV infection reflected decreased CD4+ counts at the periradicular level, however, inflammation and progression of the lesion, appeared to be comparable to the non-immunocompromised controls.     

Enamel matrix derivative (EMDOGAIN®) rapidly stimulates phosphorylation of the MAP kinase family and nuclear accumulation of smad2 in both oral epithelial and fibroblastic human cells

In our previous study, we demonstrated that porcine enamel matrix derivative (EMD) induces p21WAF1/cip1 within 8 hours and subsequently arrests the cell cycle of human oral epithelial cells in G1 phase. In contrast, EMD markedly stimulates the proliferation of gingival fibroblasts without inducing p21WAF1/cip1. To investigate the mechanism of how EMD produces these differential effects, we have focused on the initial response of these two cell types to EMD. In epithelial cell cultures, EMD stimulated cytoskeletal actin polymerization within 30 min and promoted cell adhesion in our experimental system. EMD failed to stimulate either intracellular Ca2+ mobilization or cAMP production in either cell type. In both epithelial and fibroblastic cells, EMD (25-100 microgram/ml) rapidly produced dose-dependent phosphorylation of the mitogen-activated protein kinase (MAPK) family: extracellular signal response kinase (ERK), p38-MAPK (p38-K), and c-Jun-terminal kinase/stress-activated protein kinase (JNK). However, neither inhibitors of MEK (ERK kinase) nor p38-K could block EMD's anti-proliferative action on epithelial cells. On the other hand, EMD rapidly stimulated translocation of smad2 into the nucleus in both cell types. Spurred by this finding, we assayed for TGF-beta1, a ligand for one receptor associated with smad2 activation, and detected significant levels in EMD preparations. The sum of these pharmacological findings indicates that EMD contains at least one bioactive factor, which is most probably TGF-beta1 (or TGF-beta-like substances). In conjunction with the similarities in the differential growth-modulating actions between EMD and what is known for TGF-beta, we suggest that TGF-beta might act as the principal growth regulating agent of oral fibroblastic and epithelial cell types in EMD despite being present in only low levels.     

Periodontal repair in dogs: effect of recombinant human transfornning growth factor-β1 on guided tissue regeneration

Abstract. This study evaluated alveolar bone and cementum regeneration following surgical implantation of recombinant human transforming growth factor- β₁ (rhTGF-β₁) in conjunction with guided tissue regeneration (GTR). Supraalvcolar, critical size, periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in right and left jaw quadrants in 5 beagle dogs. Alternate jaw quadrants in consecutive animals received rhTGF-β₁ in a CaCO₃/ hydroxyethyl starch carrier with GTR, or carrier with GTR alone (control), 20μg of rhTGF-/A in buffer solution was incorporated into approximately 0.8 ml of carrier for each defect scheduled to receive rhTGF-β₁. Animals were sacrificed at week 4 postsurgery and tissue blocks were harvested and processed for histo-metric analysis. Clinical healing was generally uneventful. Minor membrane exposures were observed. Defects with membrane exposure displayed an inflammatory infiltrate underneath the membrane. Bone regeneration of trabecular nature, apparent in all animals, was generally limited to the very apical aspect of the defects. Cementum regeneration was limited without obvious differences between experimental conditions. Comparing rhTGF-β to control defects, statistically significant differences were found for area (1.8±0.4 and 1.3±0.6 mm², respectively: p<0.05) and density (0.3±0.1 and 0.2±0.03. respectively: p<0.05) of alveolar bone regeneration. Observed differences are small and represent a clinically insignificant potential for enhanced regeneration in this preclinieal model. Within the limitations of study, it may be concluded that rhTGF-β₁ has a restricted potential to enhance alveolar bone regeneration in conjunction with GTR.     

HIV infection: oral lesions, CD4 + cell count and viral load in an ltalian study population

The aims of this study were to assess types and prevalence of HIV-related oral lesions and to correlate these lesions to the main laboratory parameters such as CD4+ cell count and plasma HIV-RNA. The study population consisted of 104 consecutive HIV+ patients living in Sicily (M=67, 64.4%; F=37, 35.6%; median age=35 years). CD4+ cell count and viral load were measured within 24 h of oral examination. Data were managed and analysed by Epi-Info 6.0. HIV-related oral lesions, as classified by the EC-Clearinghouse, were diagnosed in 35.6% of patients: these were of the Strongly Associated (SA) type in 22.1%, the Less Common Associated (LCA) type in 12.5%, and the Lesions Seen in HIV Infection (LS) type in 3.8%. CD4+ cell counts <200 x 10(6)/l were significantly associated only with SA lesions (P=0.03); median values of CD4+ cell count were also significantly correlated (P=0.02). Viral load, expressed both by median values of copies/ml (P=0.0001) and log10 copies/ml (P=0.0003), was significantly associated only with SA lesions. Treatment failure was significantly correlated to SA lesions (P=0.04). Besides the confirmed correlation with CD4 depletion, the strong association with a high level of viral load could make SA oral lesions a useful tool for identifying progression of HIV infection and could be of value in monitoring antiretroviral therapy.