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 i mmediate peripheral lymphocytopenias of different degree and duration. Lymphocytopenia is of short duration after the administration of immu noglobulin A CD3 mAb, but it persists much longer after the administra tion of immunoglobulin G2a CD3 mAb. Peripheral lymphocytopenia after t he administration of WT31, a murine immunoglobulin G1 TCR mAb, appears to be dependent on the polymorphism of Fc gamma Rlla. In high respond ers, lymphocytopenia is comparable to that observed after immunoglobul in G2a CD3 mAb; in low responders, no lymphocytopenia occurs. In vitro , both immunoglobulin A and immunoglobulin G2a CD3 mAbs induce immedia te activation of CD11a/CD18, with concomitant up-regulation of CD11b/C D18 on T cells, each of which is shown to be involved in the concurren t adhesion of T cells to endothelium. WT31 induces an immediate activa tion of CD11a/CD18 as well as T cell adhesion to endothelium in Fc gam ma Rlla high responders only, interestingly without changes in the lev el of expression of CD11b/CD18. We conclude that the immediate occurre nce of peripheral lymphocytopenia after the administration of CD3/TCR mAb is mediated by changes in the level of expression or avidity (or b oth) 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.