Antibodies to the T-cell receptor (CD3) induce LFA-1/Mac-1-dependent mononuclear cell adhesion to human arterial endothelium.
Monoclonal antibodies to the CD3 determinant on T lymphocytes have been used extensively as immunosuppressive agents. The T-cell receptor forms a complex with CD3 so that antibodies to CD3 mimic T-cell receptor cross-linking by human leukocyte antigens. Both CD3 and T-cell receptor cross-linking have been associated with lymphocyte activation and expression of the LFA-1 adhesion ligand, which leads to adhesion to intercellular adhesion molecule 1 immobilized on artificial surfaces. We sought to determine if anti-CD3 antibodies would increase adhesion of heart transplant recipient peripheral blood mononuclear cells to confluent human aortic endothelial cells by a similar mechanism. Peripheral blood mononuclear cells were incubated for 30 minutes with monoclonal CD3 or CD3 + CD18 antibody, before a 15-minute incubation with unstimulated human aortic endothelial cells. Mononuclear cell adhesion doubled after anti-CD3 antibody preincubation from 15.1 +/- 2.1 to 29.3 +/- 6.7 cells/high-power field (p = 0.002). This increase was abolished by coincubation with anti-CD18 (7.1 +/- 3 cells/high-power field; p = 0.0002). The major increase was the result of increased lymphocyte adhesion (3.4 +/- 0.6 to 14.8 +/- 6.7 cells/high-power field; p = 0.02); however, monocyte adhesion also increased from 11.7 +/- 1.5 to 14.5 +/- 1.6 cells/high-power field (p = 0.04). Anti-CD18 antibodies markedly reduced binding of both cell types. Cross-linking of the T-cell receptor by antibodies to CD3 causes acute adhesion of mononuclear cells (particularly lymphocytes) to arterial endothelium. Increased adhesion is mediated through CD18 (LFA-1/Mac-1).
Fyfe
A I
AI
Ahmanson-University of California, Los Angeles.
Stevenson
L W
LW
Berliner
J A
JA
Fogelman
A M
AM
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D018821:CD18 Antigens; D017252:CD3 Complex / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology*; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D017252:CD3 Complex; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D011948:Receptors, Antigen, T-Cell