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 peripheral blood mononuclear cells (PBMCs) that is not well understood. We studied 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 blocked with anti-CD18 antibodies, indicating the participation of beta 2 integrins. As this increased adhesiveness could explain the lymphopenia by adhesion of PBMCs to endothelial cells and their sequestration in some peripheral vascular beds, we studied the effect of anti-CD18 antibodies in vivo on mice injected with 145/2C11, a hamster monoclonal antibody against murine 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. Consequently, the in vivo depletion of PBMCs after administration of an anti-CD3 monoclonal antibody involves CD18-independent mechanisms, while the transient drop in polymorphonuclear cells appears to be CD18-dependent.
Kinnaert
P
P
Laboratoire Pluridisciplinaire de Recherche Experimentale Biomédicale, Faculté de Médecine de 1'Université Libre de Bruxelles, Belgium.
Pradier
O
O
Bournonville
B
B
Habrant
C
C
Goldman
M
M
Van Geertruyden
N
N
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D016853:Muromonab-CD3 / Q000494:pharmacology*; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016853:Muromonab-CD3