Evidence for involvement of superantigens in human periodontal diseases: skewed expression of T cell receptor variable regions by gingival T cells

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Abstract
Immunomodulation by periodontopathic bacteria has been implicated in the pathogenesis of inflammatory periodontal diseases. A novel class of microbial-derived T cell mitogens, referred to as superantigens, has recently been described. Superantigens are unique in that they induce a tremendous activation and expansion of specific subsets of T cells in an antigen-independent manner, thereby causing immune dysfunction. Subsets of superantigen-expanded T cells can be identified with reagents that discriminate among different families of the variable domains of the T cell antigen receptor beta-chain (V beta). Since superantigens expand one or a few of these T cell antigen receptor V beta families, T cell subsets that have been expanded by superantigens have restricted expression of one or a few V beta families. In the present study, we investigated the presence of putative superantigen-stimulated T cells in periodontitis sites, utilizing a panel monoclonal antibodies to T cell antigen receptor V beta families. Leukocytes were isolated from gingival tissues obtained from 8 periodontitis and 4 non-periodontitis patients by collagenase digestion. Three-color flow cytometric analysis of these gingival cells demonstrated that in most periodontitis patients examined, patterns of V beta expression among T cells are characteristic of superantigen stimulation, i.e., there is an elevation in the proportion of one or a few V beta families. Specifically, these analyses revealed that T cell subsets expressing V beta 5a and V beta 5b, V beta 6, V beta 8 and V beta 12 were each elevated greater than 2 standard deviations in at least one periodontitis patient compared with the mean of the non-periodontitis subjects. In some periodontitis patients, a less marked elevation of T cells that express V beta 3, V beta 5a, V beta 5b, V beta 6, V beta 8, V beta 12, and V beta 13 was noted (greater than 1 standard deviation higher than the mean of the V beta families in non-periodontics subjects). Interestingly, V beta 8+ T cells were elevated to some degree in all periodontitis patients examined. In contrast, T cells expressing V beta 2, V beta 17 and V beta 19 were not significantly different in any of the subjects studied. In most periodontitis but not non-periodontitis patients, up to 50% of all gingival T cells expressed one or a few T cell antigen receptor V beta families, suggesting that superantigens constitute a major pathway of T cell activation and expansion. Hence, our data support the hypothesis that a large proportion of T cells in periodontitis sites have been stimulated and expanded by superantigens, presumably produced by periodontitis-associated bacteria.