ROLE OF CD18-DEPENDENT AND CD18-INDEPENDENT MECHANISMS IN THE INCREASED LEUKOCYTE ADHESIVENESS AND IN THE VARIATIONS OF CIRCULATING WHITE BLOOD-CELL POPULATIONS INDUCED BY ANTI-CD3 MONOCLONAL-ANTIBODIES

Anti-CD3 antibodies induce a quick and profound depletion of periphera l blood mononuclear cells (PBMCs) that is not well understood. We stud ied the effect of OKT3, a mouse monoclonal antibody against the human CD3 complex, on the in vitro adhesion of human PBMCs to monolayers of fresh and fixed human umbilical vein endothelial cells (HUVECs), OKT3 induced an increased adhesiveness of PBMCs. This phenomenon was blocke d with anti-CD18 antibodies, indicating the participation of beta 2 in tegrins. As this increased adhesiveness could explain the lymphopenia by adhesion of PBMCs to endothelial cells and their seques tration in some peripheral vascular beds, we studied the effect of anti-CD18 anti bodies in vivo on mice injected with 145/2C11, a hamster monoclonal an tibody against murine CD3. Mice treated with 145/2C11 presented with a transient granulocytopenia and a sustained reduction in PBMCs. A mono clonal anti-CD18 antibody prevented the granulocytopenia but had no ef fect on the drop in PBMCs. Consequently, the in vivo depletion of PBMC s after administration of an anti-CD3 monoclonal antibody involves CD1 8-independent mechanisms, while the transient drop in polymorphonuclea r cells appears to be CD18-dependent.