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*
Department of Biology and
Departments of Pathology and Immunology, Yale University, New Haven, CT 06510
We compared costimulatory signals provided by 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-
, 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- production by naive T cells. ECs do not secrete IL-12, and
addition of exogenous IL-12 enables ECs to costimulate IFN- 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.
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