Human endothelial cells effectively costimulate cytokine production by, but not differentiation of, naive CD4+ T cells

We compared costimulatory signals provided hy human endothelial cells (ECs) to those provided by conventional bone marrow-derived APCs, i.e., peripheral blood-adherent mononuclear cells (PBAMCs), by measuring their effects on cytokine production by naive or memory CD4(+) T cells stimulated by PHA, In these assays, ECs effectively costimulate secretion of IL-2, IFN-gamma, and IL-4 from both naive and memory CD4(+) T cells, quantified by ELISA or intracellular cytokine staining, ECs, which lack B7 molecules, use predominantly leukocyte-function associated Ag 3 (LFA-3) to provide costimulation, ECs are comparable to or better than PBAMCs, which use both the LFA-3 and B7 molecules, at costimulating IL-2 and IL-4 production. ECs are less effective than PBAMCs at costimulating IFN-gamma production by naive T cells, ECs do not secrete IL-12, and addition of exogenous IL-12 enables ECs to costimulate IFN-gamma at a level comparable to that observed with PBAMCs, ECs do not promote differentiation of naive T cells to Th1-like cells, whereas PBAMCs do, Again, addition of exogenous IL-12 enables ECs to do so. Transfection of ECs to express B7-1 or B7-2 is less effective than IL-12 supplementation for restoring these responses, These experiments suggest that a deficiency in costimulation due to lack of B7 molecule expression does not fully explain the inability of ECs to activate resting naive CD4(+) T cells.