Single-cell analysis of costimulation by B cells, endothelial cells, and fibroblasts demonstrates heterogeneity in responses of CD4(+) memory T cells

Human endothelial cells (EC) express MHC class II molecules in vivo and are likely to be involved in presentation of antigens to CD4(+) T cells. We ex amined, at the single-cell level, EC presentation of superantigens to resti ng CD4(+) memory T cells. Within 2 h of adherence to class II+ EC early T c ell activation is evidenced by translocation of nuclear factor of activated T cells (NFAT), surface expression of CD69, and synthesis of IFN-gamma and IL-2. Naive T cells are not activated. T cell activation is dependent on t he prior induction of MHC class II molecules on EC and is blocked by antibo dies to LFA-S (CD58). Our data place EC along a spectrum of antigen-present ing ability. Activated B cells and macrophages trigger more cells to expres s cytokines than do EC and at lower antigen concentrations; EC are in turn, superior to fibroblasts or smooth muscle cells. Furthermore, the concept o f activation thresholds for cytokine synthesis within T cells also extends to earlier activation events: NFAT translocation is relatively easy to trig ger, as is CD69 expression; fewer cells can be triggered to express IFN-gam ma and fewer still to express IL-2. EC may, therefore, contribute to a grad ed immune response by inducing qualitatively and quantitatively different r esponses than professional APC. (C) 1999 Academic Press.