Adult periodontitis has been conceptualized as a chronic inflammatory disease. It is initiated by the accumulation of bacterial plaque within the gingival sulcus. The host response to these microbial antigens leads to the elimination of these organisms, but simultaneously causes extensive destruction of the collagenous connective tissues matrix, as well as loss of the supporting alveolar bone. Besides microbial antigens, evidence is mounting which supports the concept that some endogenous antigens may function in a pathogenic role. Studies have documented elevated levels of immunoglobulin directed against various host proteins in inflamed gingival tissue. These include antibodies directed against aggregated IgG, double stranded DNA, as well as types I and III collagen. Thus, high levels of antibody targeted against various host components in inflamed gingival tissue suggest an interplay between periodontal infection and autoimmunity. There is a particular B lymphocyte lineage (CD5/LY1/B1) which has a propensity for secreting high levels of autoantibody. Interestingly, augmented numbers of these B cells have been detected within inflamed gingival tissue. A particular cytokine, interleukin 10 (IL-10), has been reported to selectively favor the development of this B cell lineage. Therefore, the objective of this proposal is to determine whether IL-10 is elevated in inflamed gingival tissue and if it can potentiate the production of anti-collagen antibodies by these CD5 positive B cells. Increased levels of other cytokines have been noted within diseased periodontal tissue. These studies support the regulatory role of specific cytokines, such as IL-5 and IL-6, in promoting polyclonal B cell activation and augmented IgG and IgA production in inflamed gingival tissue. Within the emerging paradigm that perceives adult periodontitis as a disease characterized by """"""""hyperactive"""""""" B lymphocyte function coupled with an altered local cytokine profile, the induction of autoantibodies could be another component to this lesion. Our preliminary results demonstrate that gingival mononuclear cells extracted from adult periodontitis patients constitutively produce IL-10. Hence, we will investigate whether IL-10 plays an important role in promoting the expansion of CD5 positive B cells, and if IL-10 enhances the production of IgG anti-collagen antibodies by this B lymphocyte lineage. This proposal ill help to define the role which the autoimmune response plays in the pathogenesis of adult periodontitis.
| Stein, S H; Hart, T E; Hoffman, W H et al. (1997) Interleukin-10 promotes anti-collagen antibody production in type I diabetic peripheral B lymphocytes. J Periodontal Res 32:189-95 |
