IMMUNOPATHOLOGICAL ACTIVITIES OF EXTRACELLULAR PRODUCTS OF STREPTOCOCCUS-MITIS, PARTICULARLY A SUPERANTIGENIC FRACTION

Previously, we prepared extracellular products, fractions F-l and F-2 of Streptococcus mitis 108, an isolate from the tooth surface of an in fant, and showed that F-l exhibited inflammatory cytokine-inducing act ivities, In the present study, we present evidence that fraction F-2 i nduced human T-cell proliferation in the presence of irradiated human peripheral blood mononuclear cells and selectively activated T cells b earing V beta 2 and V beta 5.1 in the T-cell receptor. F-l, on the oth er hand, stimulated human gingival fibroblasts to support the T-cell p roliferation in the same way as human gamma interferon or Prevotella i ntermedia lipopolysaccharide (LPS). Fraction F-l also primed gingival fibroblasts to support the production of interleukin-2 and gamma inter feron by the T cells upon stimulation with F-2. Human gingival fibrobl asts stimulated with fraction F-l, like those stimulated by P. interme dia 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 antib ody inhibited T-cell proliferation in response to F-2, probably throug h inactivating the accessory function of HLA-DR-bearing fibroblasts. T cells activated with F-2 in the presence of irradiated peripheral blo od mononuclear cells exhibited definite cytotoxic effects against fibr oblasts and squamous carcinoma cells originating from human oral tissu es. These findings are strongly suggestive of an association of extrac ellular products of viridans streptococci with pathogenesis of oral mu cosal diseases, particularly those disorders in gingiva which are acco mpanied by heavy infiltration of T cells.