Signaling by vascular cell adhesion molecule‐1 (VCAM‐1) through VLA‐4 promotes CD3‐dependent T cell proliferation

Vascular cell adhesion molecule, VCAM‐1, is an adhesion molecule expressed on activated endothelium thought to play a role in leukocyte migration to sites of inflammation. VCAM‐1 adheres to leukocytes through the VLA‐4 integrin. Recombinant soluble VCAM‐1 (rsVCAM) and anti‐CD3 mAb OKT3 were utilized to address the role of the VCAM‐1/VLA‐4 pathway in antigen‐dependent T cell activation. Monocyte‐depleted T cells proliferated upon exposure to co‐immobilized OKT3 and rsVCAM but to neither alone. In contrast, an anti‐VLA‐4 mAb HP1/2 failed to co‐activate with OKT3, despite the fact that both rsVCAM and HP1/2 support T cell adhesion comparably. These data indicate that adhesive function is not sufficient for co‐stimulatory activity. They also reveal that VCAM‐1 may play a role in regulating T cell immune responses as well as migration in vivo.