Possible pathogenic effect of Streptococcus mitis super antigen on oral epithelial cells

口腔中的草绿色菌和非溶血性链球菌被认为与某些口腔疾病的发生有关。然而，很少有人知道这些链球菌的胞外产物的致病作用。最近，我们从牙齿表面分离的缓症链球菌108的培养上清液中制备了超抗原组分F-2。在这项研究中，我们研究了人外周血T细胞与F-2激活口腔上皮细胞的细胞毒性作用。用F-2活化的T细胞对人口腔鳞癌HO-1-N-1细胞有明显的细胞毒作用，并随F-2浓度的增加而增强。用干扰素γ预处理增加了HO-1-N-1细胞对F-2活化细胞的细胞毒性作用的敏感性。从HO-1-N-1细胞中分离F-2活化的T细胞时，未观察到细胞毒性作用。此外，靶细胞和效应细胞共培养物的上清液对HO-1-N-1细胞没有细胞毒性作用。F-2激活的T细胞对HO-1-N-1细胞的细胞毒性被单克隆抗体（MAbs）CD 11 α显著抑制，尽管该MAbs对F-2激活的T细胞增殖有微弱抑制。另一方面，细胞毒性弱抑制与抗人类白细胞抗原（HLA）-DR和CD 2的单克隆抗体，而T细胞增殖活性强烈抑制这些单克隆抗体。这些结果表明，F-2依赖性T细胞介导的细胞毒性的发生方式不同于T细胞增殖与F-2，和杀死与F-2激活的T细胞的靶细胞，淋巴细胞功能相关抗原-1（LFA-1）和细胞间粘附分子-1（ICAM-1）之间的相互作用是至关重要的。

Viridans and non-hemolytic streptococci in oral cavity have been suggested to be involved in the occurrence of some oral disorders. However, little is known about the pathogenic roles of extracellular products of these streptococci. Recently, we prepared a superantigenic fraction F-2 from the culture supernatant of Streptococcus mitis 108 isolated from the tooth surface. In this study, we examined the cytotoxic effects of human peripheral blood T cells activated with the F-2 on oral epithelial cells. T cells activated with F-2 exhibited definite cytotoxic effects against the human squamous carcinma HO-1-N-1 cells derived from the oral mucosa and this cyytotoxic effect was increased in a dose-dependent manner by sddition of F-2. Pretreatment with interferon gamma increased the susceptibility of the HO-1-N-1 cells to the cytotoxic effects of F-2-activated cells. No cytotoxic effects were observed when the F-2-activated T cells were separated from the HO-1-N-1 cells. Furthermore, supernatants of the cocultures of target and effect or cells exhibited no cytotoxic effects on HO-1-N-1 cells. The cytotoxicity of the F-2-activated T cells against HO-1-N-1 cells was markedly inhibited by monoclonal antibodies (MAbs) CD11alpha, although T cell proliferation with F-2 was weakly inhibited by this MAbs. On the other hand, the cytotoxicity was weakly inhibited with MAbs against human leukocyte antigen (HLA)-DR and CD2, whereas the T cell proliferative activity were strongly inhibited by these MAbs. These findings suggest that the F-2-dependent T cell-mediated cytotoxicity occurred in a manner different from T cell proliferation with F-2, and to kill the target cells with F-2-activated T cells, the interaction between lymphocyte-function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) was crucial.