HUMAN ENDOTHELIAL-CELLS EFFECTIVELY COSTIMULATE CYTOKINE PRODUCTION BY, BUT NOT DIFFERENTIATION OF, NAIVE CD4(-CELLS() T)

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 t heir effects on cytokine production by naive or memory CD4(+) T cells stimulated by PHA, In these assays, ECs effectively costimulate secret ion of IL-2, IFN-gamma, and IL-4 from both naive and memory CD4(+) T c ells, quantified by ELISA or intracellular cytokine staining, ECs, whi ch 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 costimulat ing IL-2 and IL-4 production. ECs are less effective than PBAMCs at co stimulating 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 p romote differentiation of naive T cells to Th1-like cells, whereas PBA MCs do, Again, addition of exogenous IL-12 enables ECs to do so. Trans fection of ECs to express B7-1 or B7-2 is less effective than IL-12 su pplementation for restoring these responses, These experiments suggest that a deficiency in costimulation due to lack of B7 molecule express ion does not fully explain the inability of ECs to activate resting na ive CD4(+) T cells.