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Immunopathological activities of extracellular products of Streptococcus mitis, particularly a superantigenic
K Matsushita1, W Fujimaki, H Kato
1Department of Microbiology and Immunology, Kagoshima University Dental School, Japan.
Abstract:
Previously, we prepared extracellular products, fractions F-1 and F-2 of Streptococcus mitis 108, an isolate from the tooth surface of an infant, and showed that F-1 exhibited inflammatory cytokine-inducing activities. In the present study, we present evidence that fraction F-2 induced human T-cell proliferation in the presence of irradiated human peripheral blood mononuclear cells and selectively activated T cells bearing V beta 2 and V beta 5.1 in the T-cell receptor. F-1, on the other hand, stimulated human gingival fibroblasts to support the T-cell proliferation in the same way as human gamma interferon or Prevotella intermedia lipopolysaccharide (LPS). Fraction F-1 also primed gingival fibroblasts to support the production of interleukin-2 and gamma interferon by the T cells upon stimulation with F-2. Human gingival fibroblasts stimulated with fraction F-1, like those stimulated by P. intermedia LPS and human gamma interferon, exhibited human leukocyte antigen (HLA)-DR mRNA expression and cell surface HLA-DR molecules as detected by enzyme-linked immunosorbent assay. An anti-HLA-DR monoclonal antibody inhibited T-cell proliferation in response to F-2, probably through inactivating the accessory function of HLA-DR-bearing fibroblasts. T cells activated with F-2 in the presence of irradiated peripheral blood mononuclear cells exhibited definite cytotoxic effects against fibroblasts and squamous carcinoma cells originating from human oral tissues. These findings are strongly suggestive of an association of extracellular products of viridans streptococci with pathogenesis of oral mucosal diseases, particularly those disorders in gingiva which are accompanied by heavy infiltration of T cells.
Insights
Extracellular products from Streptococcus mitis stimulate T cells and gingival fibroblasts, potentially contributing to oral mucosal diseases. These bacterial products activate immune cells and influence cell interactions involved in pathogenesis.
Area of Science:
- Oral microbiology
- Immunology
- Cell biology
Background:
- Streptococcus mitis extracellular products (F-1 and F-2) were previously shown to induce inflammatory cytokines.
- Fraction F-1 exhibited inflammatory cytokine-inducing activities.
Purpose of the Study:
- To investigate the immunomodulatory effects of Streptococcus mitis extracellular products F-1 and F-2 on human T cells and gingival fibroblasts.
- To explore the role of these products in oral mucosal disease pathogenesis.
Main Methods:
- Fraction F-2 induced human T-cell proliferation and activated T cells expressing specific T-cell receptor V beta chains.
- Fraction F-1 stimulated gingival fibroblasts, enhancing T-cell proliferation and priming them for cytokine production.
- Human leukocyte antigen (HLA)-DR expression on fibroblasts was analyzed and its role in T-cell proliferation was assessed using monoclonal antibodies.
- Cytotoxic effects of activated T cells on oral tissue cells were evaluated.
Main Results:
- Fraction F-2 promoted T-cell proliferation and activated T cells with V beta 2 and V beta 5.1 T-cell receptors.
- Fraction F-1 induced gingival fibroblast activation, mimicking effects of gamma interferon and Prevotella intermedia lipopolysaccharide (LPS).
- Fibroblast activation by F-1 enhanced T-cell production of interleukin-2 and gamma interferon upon F-2 stimulation.
- HLA-DR expression on fibroblasts, induced by F-1, was crucial for F-2-mediated T-cell proliferation.
- Activated T cells displayed cytotoxic activity against oral fibroblasts and squamous carcinoma cells.
Conclusions:
- Extracellular products of Streptococcus mitis modulate immune responses, involving T-cell activation and fibroblast interaction.
- These bacterial products may play a role in the pathogenesis of oral mucosal diseases, especially gingival disorders characterized by T-cell infiltration.
- The findings highlight a potential link between viridans streptococci and inflammatory oral conditions.