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

口腔内的绿绿菌和非溶血性链球菌被认为与一些口腔疾病的发生有关。然而，对这些链球菌的细胞外产物的致病作用知之甚少。最近，我们从牙齿表面分离的炎链球菌108培养上清中制备了超抗原片段F-2。在这项研究中，我们检测了被F-2激活的人外周血T细胞对口腔上皮细胞的细胞毒性作用。用F-2激活的T细胞对人口腔粘膜的HO-1-N-1细胞表现出明确的细胞毒性作用，并且这种细胞毒性作用以剂量依赖的方式随着F-2的添加而增加。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。将f -2活化的T细胞与HO-1-N-1细胞分离后，未观察到细胞毒性作用。此外，靶细胞和效应细胞共培养的上清液对HO-1-N-1细胞没有细胞毒性作用。单克隆抗体CD11alpha可明显抑制F-2活化T细胞对HO-1-N-1细胞的细胞毒性，但该单克隆抗体可微弱抑制F-2活化T细胞的增殖。另一方面，抗人白细胞抗原(HLA)-DR和CD2的单克隆抗体能微弱抑制细胞毒性，而T细胞的增殖活性则被这些单克隆抗体强烈抑制。这些发现表明，F-2依赖性T细胞介导的细胞毒性以不同于F-2激活T细胞增殖的方式发生，并且为了用F-2激活的T细胞杀死靶细胞，淋巴细胞功能相关抗原-1 （LFA-1）和细胞间粘附分子-1 （ICAM-1）之间的相互作用至关重要。

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.