Induction of Germinal Centers by MMTV Encoded Superantigen on B Cells

It has not been established whether an endogenous superantigen (SAg) expressed on B cells can induce germinal centers (GCs). An interesting model is that of mammary tumor virus encoded viral SAgs, which induce vigorous T cell proliferation and are predominantly expressed on activated B cells. We have used this model to analyze the possibility that direct stimulation of Mtv7+ DBA/2 B cells by vSAg-responsive (Vβ6+) BALB/c T cells can give rise to GCs. Injection of BALB/c SCID mice iv with 2 × 106 DBA/2 B cells, together with LPS, followed by 2 × 106 BALB/c T cells induces numerous large splenic GCs within 3–5 days. The GCs are still large on day 7, but are very much reduced by day 10. B cell activation with LPS is needed for this effect. These GCs form in spite of the apparent absence of follicular dendritic cells (FDCs) as judged by staining for several FDC surface markers. Control mice receiving either BALB/c T or DBA/2 B cells + LPS alone or DBA/2 T + B cells + LPS fail to exhibit any GCs on days 3–7. Numerous small clusters of PNA+ cells, but few large GCs are observed when TNF-R(p55)-Ig is also injected, whereas LTβR-Ig treatment impeded the formation of aggregations of these cells even further, leaving scattered PNA+ single cells and very small clumps throughout the white pulp of the spleens. Anti-TNFα had no effect. These results suggest that endogenous vSAg mediated GC formation is independent of antigen trapping by FDCs

Aggregatibacter actinomycetemcomitans Infection Enhances Apoptosis In Vivo through a Caspase-3-Dependent Mechanism in Experimental Periodontitis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)The purpose of this study was to test the hypothesis that diabetes aggravates periodontal destruction induced by Aggregatibacter actinomycetemcomitans infection. Thirty-eight diabetic and 33 normal rats were inoculated with A. actinomycetemcomitans and euthanized at baseline and at 4, 5, and 6 weeks after inoculation. Bone loss and the infiltration of polymorphonuclear leukocytes (PMNs) in gingival epithelium were measured in hematoxylin-eosin-stained sections. The induction of tumor necrosis factor alpha (TNF-alpha) was evaluated by immunohistochemistry and of apoptotic cells by a TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay. After A. actinomycetemcomitans infection, the bone loss in diabetic rats was 1.7-fold and the PMN infiltration 1.6-fold higher than in normoglycemic rats (P < 0.05). The induction of TNF-alpha was 1.5-fold higher and of apoptotic cells was up to 3-fold higher in diabetic versus normoglycemic rats (P < 0.05). Treatment with a caspase-3 inhibitor significantly blocked noninflammatory cell apoptosis induced by A. actinomycetemcomitans infection in gingival epithelium and connective tissue (P < 0.05). These results provide new insight into how diabetes aggravates A. actinomycetemcomitans-induced periodontal destruction in rats by significantly increasing the inflammatory response, leading to increased bone loss and enhancing apoptosis of gingival epithelial and connective tissue cells through a caspase-3-dependent mechanism. Antibiotics had a more pronounced effect on many of these parameters in diabetic than in normoglycemic rats, suggesting a deficiency in the capacity of diabetic animals to resist infection.80622472256NIDCR [DE018307, DE017732]Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)NIDCR [DE018307, DE017732

A.actinomycetemcomitans-induced periodontal disease promotes systemic and local responses in rat periodontium

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Aim: To characterize the histologic and cellular response to A. actinomycetemcomitans (Aa) infection. Material and Methods: Wistar rats infected with Aa were evaluated for antibody response, oral Aa colonization, loss of attachment, PMN recruitment, TNF-a in the junctional epithelium and connective tissue, osteoclasts and adaptive immune response in local lymph nodes at baseline and 4, 5 or 6 weeks after infection. Some groups were given antibacterial treatment at 4 weeks. Results: An antibody response against Aa occurred within 4 weeks of infection, and 78% of inoculated rats had detectable Aa in the oral cavity (p 0.05). Conclusion: Aa infection stimulated a local response that increased numbers of PMNs and TNF-a expression in the junctional epithelium and loss of attachment. Both TNF-a expression in JE and loss of attachment was reversed by antibiotic treatment. Aa infection also increased TNF-a in the connective tissue, osteoclast numbers and CD8 + T cells in lymph nodes. The results link Aa infection with important characteristics of periodontal destruction.394333341NIDCR [DE017732, DE018307]Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)NIDCR [DE017732, DE018307