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

用重组人干扰素-r刺激人脐静脉内皮细胞(HUVEC)，观察TSST-1、SEA及相关外毒素对HUVEC活化T细胞过程中HLAII类分子、中毒性休克综合征毒素-1(TSST-1)和葡萄球菌肠毒素A(SEA)结合活性及辅助细胞(AC)活性的影响。重组人干扰素-r在10~3000U/ml范围内刺激人脐静脉内皮细胞72h，可表达HLAII类分子。表达强度依赖于干扰素-r的浓度。人脐静脉内皮细胞经1000U/ml的干扰素-r刺激72h后，可与I-TSST-1结合，并可被未标记的相应毒素和抗DR/DP单抗阻断。这种活性不被多聚甲醛固定所阻断。干扰素-r刺激的人脐静脉内皮细胞在几种细菌外毒素刺激下产生IL-2的能力表现为AC活性。其活性可被抗DR/DP单抗阻断。鉴于TSST-1和SES直接与人T细胞表面的HLAII类分子结合，并与AC上的HLAII类分子结合而激活人T细胞，在毒素诱导的T细胞活化中上述活性的获得很可能是通过表达HLAII类分子来实现的。血管内皮细胞可能在急性全身性疾病TSS患者的病理变化中起重要作用。

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.