ENDOTHELIAL-CELLS PROMOTE ANTI-CD3-INDUCED T-CELL PROLIFERATION VIA CELL-CELL CONTACT MEDIATED BY LFA-1 AND CD2

T-cell activation requires not only T-cell receptor (TCR) engagement a nd subsequent TCR/CD3 cross-linking, but also one or more secondary ac tivation signals generated by accessory cells (AC). We investigated th e accessory function of endothelial cells (EC) in an in vitro model fo r T-cell activation where the first cross-linking signal was delivered to peripheral human T lymphocytes by either immobilized anti-CD3 mono clonal antibody (MoAb) or by PHA. In a previous report, we showed that EC provided a potent costimulatory signal in this model system. We ha ve now analysed the nature of the EC-derived costimulatory signal by t esting whether EC could be substituted by cytokines, by studying the e ffect of EC fixation and by testing the involvement of a number of adh esion molecules. Our findings indicate that EC accessory function is m ediated mainly by membrane-bound factors. The nature of these membrane -bound factors was analysed by studying the inhibitory properties of a series of MoAbs directed against several adhesion molecules. Antibodi es directed against CD44, E-selectin, CD31, CD26, B7/BB1, VLA-4 or VCA M-1 were not inhibitory. However, an inhibition, was clearly observed with antibodies against LFA-1 and CD2. Remarkably, this inhibition was not found with MoAbs to their respective counterstructures ICAM-1 and LFA-3. In summary, we postulate that both LFA-1/ICAM-1, and CD2/LFA3 interactions are involved in EC accessory function, although the role of the EC-associated adhesion partners is not fully understood.