Different CD3/T cell receptor monoclonal antibodies have distinct capacities to induce adhesion of T lymphocytes to endothelium.
Murine CD3/T cell receptor (TCR) monoclonal antibodies (mAbs) induce immediate peripheral lymphocytopenias of different degree and duration. Lymphocytopenia is of short duration after the administration of immunoglobulin A CD3 mAb, but it persists much longer after the administration of immunoglobulin G2a CD3 mAb. Peripheral lymphocytopenia after the administration of WT31, a murine immunoglobulin G1 TCR mAb, appears to be dependent on the polymorphism of Fc(gamma)RIIa. In high responders, lymphocytopenia is comparable to that observed after immunoglobulin G2a CD3 mAb; in low responders, no lymphocytopenia occurs. In vitro, both immunoglobulin A and immunoglobulin G2a CD3 mAbs induce immediate activation of CD11a/CD18, with concomitant up-regulation of CD11b/CD18 on T cells, each of which is shown to be involved in the concurrent adhesion of T cells to endothelium. WT31 induces an immediate activation of CD11a/CD18 as well as T cell adhesion to endothelium in Fc(gamma)RIIa high responders only, interestingly without changes in the level of expression of CD11b/CD18. We conclude that the immediate occurrence of peripheral lymphocytopenia after the administration of CD3/TCR mAb is mediated by changes in the level of expression or avidity (or both) of adhesion molecules on T cells, whereas the persistence of this lymphocytopenia depends on the isotype of the CD3/TCR mAb and on the presence of suitable Fc receptors.
Buysmann
S
S
Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
Schellekens
P T
PT
Tax
W J
WJ
ten Berge
I J
IJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008231:Lymphopenia / Q000209:etiology / Q000378:metabolism; D051379:Mice; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D017452:Receptors, IgG / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D017452:Receptors, IgG