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

Abstract

Abstract Anti-CD3 antibodies in duce a quick and profound depletion of peripheral blood mononu-clear cells (PBMCs) that is not well understood. We studied the effect of OKT3, a mouse monoclonal anti body against the human CD3 com plex, on the in vitro adhesion of human PBMCs to monolayers of fresh and fixed human umbilical vein en-dothelial cells (HUVECs). OKT3 induced an increased adhesiveness of PBMCs. This phenomenon was blocked with anti-CD 18 antibodies, indicating the participation of β2 integrins. As this increased adhesiveness could explain the lym-phopenia by adhesion of PBMCs to endothelial cells and their sequestration in some peripheral vascular beds, we studied the effect of anti-CD 18 antibodies in vivo on mice injected with 145/2C11, a hamster monoclonal antibody against mu-rine CD3. Mice treated with 145/2C11 presented with a transient granulocytopenia and a sustained reduction in PBMCs. A monoclonal anti-CD18 antibody prevented the granulocytopenia but had no effect on the drop in PBMCs. Conse quently, the in vivo depletion of PBMCs after administration of an anti-CD3 monoclonal antibody in volves CD18-independent mecha nisms, while the transient drop in polymorphonuclear cells appears to be CD18-dependent.