Type 1-diabetes is caused by autoimmune attack of the pancreatic b-cell islets mediated by diabetogenic T cells, resulting in insufficient insulin production and hyperglycemia. Like in type 2 diabetes, type-1 diabetics develop periodontal infections (i.e. periodontitis) more frequently than non-diabetics do and clinical and epidemiological studies support that type-1 diabetes is a risk factor for periodontitis. Further, periodontitis has recently been shown to be associated with an increased risk for certain systemic disorders and may interactively modulate metabolic outcomes of diabetes. Around $10-15 billion dollars per year are spent on periodontal diagnosis and treatment including the replacement of affected teeth in North America. However, studies regarding the fundamental """"""""immunological basis"""""""" associated with the increased risk for severe periodontal breakdown in type 1 diabetes are lacking and practically unknown. The Non Obese Diabetic (NOD) mouse shares many clinical features of human type-1 diabetes and is an excellent animal model for studying type-1 diabetes. The current proposal uses the NOD mice to investigate the contribution of autoimmunity to periodontal anti-bacterial immunity and the specific aims are to study I) the contribution of the osteoclastogenic cytokine, osteoprotegerin-ligand (OPG-L,) and Th1/Th2 cytokines produced by oral microorganism-specific CD4+ T cells for periodontal inflammation and destruction induced by a well-know periodontal pathogen A. actinomycetemcomitans (Aa) in diabetic, non-diabetic and pre-diabetic NOD mice; ii) the frequency of Aa-reactive periodontal CD4+ T cells in diabetic, non-diabetic and pre-diabetic NOD mice; ii) the frequency of Aa-reactive periodontal CD4+ cells in diabetic, non -diabetic and pre-diabetic NOD mice during periodontal inflammation and destruction and iii) whether there is a significant role for the humoral immune response during periodontal infection under autoimmune conditions in diabetic NOD mice. The new information generated will provide the biological relevance of OPG-L in mediating periodontal destruction in type-1 diabetes and ii) the relationship between OPG-L expression, TH1/TH2 cytokine profile and humoral immunity for periodontal breakdown in type-1 diabetes. Importantly, the proposed research will provide the first clarification whether there is immunological basis for severe periodontal breakdown in type-1 diabetes. Thus, this tern will facilitate our understanding of the links and studying the mechanisms of periodontal infection type-1 diabetes.
