T-CELL INTERACTION WITH ICAM-1-DEFICIENT ENDOTHELIUM IN-VITRO - ESSENTIAL ROLE FOR ICAM-1 AND ICAM-2 IN TRANSENDOTHELIAL MIGRATION OF T-CELLS

Transendothelial migration is a crucial step in the complex process of lymphocyte extravasation during lymphocyte homing, immunosurveillance and inflammation. However, little is known about the precise role of cell adhesion molecules (CAM) involved in this particular event. To de fine the CAM involved in T cell adhesion versus transendothelial migra tion, we have previously established an in vitro transendothelial migr ation system using mouse T cells and mouse endothelioma cells. We demo nstrate here that, using ICAM-1-deficient endothelioma cells derived f rom ICAM-1 mutant mice, transendothelial migration of T cells was inhi bited to a much greater extent when compared to migration across wild- type cells treated with a blocking anti-ICAM-1 monoclonal antibody. Th is unexpected result:was confirmed by a rescue experiment using retrov iral transfer of wild-type ICAM-1 into ICAM-1-deficient endothelial ce lls. Additional experiments showed that, in the absence of functional ICAM-1, only ICAM-2 was involved in transendothelial migration, but no t PECAM-1, VCAM-1, or E-selectin. Taking this novel approach, we show that ICAM-I and ICAM-2 are essential for transendothelial migration of T cells.