CD99 (E2) up‐regulates α 4β 1‐dependent T cell adhesion to inflamed vascular endothelium under flow conditions

CD99/E2 is an integral transmembrane protein which forms, together with Xga, a distinct family whose genes are located in the pseudoautosomal region. The number of T cells that firmly bound to vascular endothelial cells under physiological shear stress increased 2–14-fold upon CD99 stimulation, and bound cells became much more resistant to detachment forces and spread. T cell arrest occurred within 1 min and was dependent on the α4β1-VCAM-1 pathway. In contrast, the αLβ2-ICAM-1 pathway remained unactivated. This was observed with T cell lines and with activated peripheral blood lymphocytes, and was limited within the resting peripheral CD4+ T cells to the memory subset, while virgin cells were unaffected. This discloses a stepwise regulation of the T cell extravasation cascade.