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 and subsequent TCR/CD3 cross-linking, but also one or more secondary activation signals generated by accessory cells (AC). We investigated the accessory function endothelial cells (EC) in an in vitro model for T-cell activation where the first cross-linking signal was delivered to peripheral human T lymphocytes by cither immobilized anti-CD3 monoclonal antibody (MoAb) or by PHA. In a previous report, we showed that EC provided a potent costimulatory signal in this model system. We have now analysed the nature of the EC-derived costirnulatory signal by testing whether EC could be substituted by cy lokines. by studying the effect of EC fixation and by testing the involvement of a number of adhesion molecules. Our findings indicate that EC accessory function is mediated 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. Antibodies directed against CD44, E-selectin, CD31, CD26, B7/BBI, VLA-4 or VCAM-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-l/ICAM-1, and CD2 LFA-3 interactions are involved in EC accessory function, although the role of the EC-associated adhesion partners is not fully understood.