Analysis of T cell activation by bacterial extoxins bearing MHC class II-binding activity

用重组人γ-干扰素（IFN-γ）刺激人脐静脉内皮细胞（HUVEC），观察其表达HLA Ⅱ类分子、中毒性休克综合征毒素1（TSST-1）、金黄色葡萄球菌肠毒素A（SEA）结合活性及辅助细胞（AC）活性。用10 ~ 3000 U/ml的重组人IFN-γ刺激HUVEC 72 h，表达HLA Ⅱ类分子。表达强度与IFN-γ浓度有关。用1000 U/ml IFN-γ刺激HUVEC 72 h后<125>，其与TSST-1和SEA的结合被未标记的相应毒素和抗DR/DP的mAb阻断。活性不被多聚甲醛固定所阻断。IFN-γ刺激的HUVEC在用几种细菌外毒素刺激的人外周T细胞中的IL-2产生中表现出AC活性。抗DR/DP单克隆抗体可阻断该活性。鉴于TSST-1和SE直接结合HLA II类分子并激活AC上与HLA II类分子相关的人T细胞的事实，在毒素诱导的T细胞激活中获得上述活性可能是由HLA II类分子的表达介导的。血管内皮细胞似乎在急性全身性疾病TSS患者的病理变化发展中起重要作用。

Human umbilical vascular endothelial cells (HUVEC) stimulated with recombinant human IFN-r were inveatigated for expression of HLA class II molecules, toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A(SEA)-binding activity and accessory cell (AC) activity in T cell activation by TSST-1, SEA and related exotoxins. HUVEC stimulated with recombinant human IFN-r ranging from 10 to 3000 U/ml for 72 h express HLA class II molecules. Intensity of the expression was dependent on the concentration of IFN-r. HUVEC stimulated with 1000 U/ml of IFN-r for 72 h exhibited ^<125>I-TSST-1 and SEA-binding that was blocked by the unlabeled coresponding toxins and mAb to DR/DP. The activity was not blocked by paraformaldehyde fixation. The IFN-r-stimulated HUVEC exhibited AC activity in IL-2 production in human peripheral T cells stimulated with the several bacterial exotoxins. The activity was blocked by mAb to DR/DP. In view of the facts that TSST-1 and SEs bind directly to HLA class II molecules and activate human T cells in association with HLA class II molecules on AC, it is likely that the acquisition of the above activities in the toxin-induced T cell activation is mediated by the expression of HLA class II molecules. It seems likely that vascular endothelial cells play an important role in the development of pathological changes in patients suffering an acute and systemic illness TSS.