ACTIVATION OF HUMAN VASCULAR ENDOTHELIAL-CELLS BY IFN-GAMMA - ACQUISITION OF HLA CLASS-II EXPRESSION, TSST-1-BINDING ACTIVITY AND ACCESSORY ACTIVITY IN T-CELL ACTIVATION BY THE TOXIN

Human umbilical vascular endothelial cells (HUVEC) stimulated with recombinant human IFN-gamma were investigated for expression of HLA class II molecules, toxic shock syndrome toxin-1 (TSST-1)-binding activity and accessory cell (AC) activity in TSST-1-induced T cell activation. HUVEC stimulated with recombinant human IFN-gamma ranging from 10 to 1,000 units/ml for 72 h express HLA class II molecules. Intensity of the expression was dependent on the concentration of IFN-gamma. HUVEC stimulated with 1,000 units/ml of IFN-gamma for 72 h exhibited I-125-TSST-1-binding that was blocked by the unlabeled toxin and monoclonal antibodies (mAb) to DR/DP. The activity was not removed by paraformaldehyde fixation. The IFN-gamma-stimulated HUVEC exhibited AC activity in TSST-1-induced IL-2 production by T cells from human peripheral blood mononuclear cells. The activity was blocked by mAb to DR. The above two activities were also observed in L cells transfected with DR2 genes but not in the unstimulated HUVEC and control L cells. In view of the fact that TSST-1 binds directly to HLA class II molecules and activates human T cells in association with HLA class II molecules on AC, it is likely that the acquisition of TSST-1-binding activity and AC activity in the toxin-induced T cell activation is mediated by the expression of HLA class II molecules. Vascular endothelial cells may play an important role in the development of pathological changes in TSS patients.