BIPHASIC GRANULOCYTOPENIA AFTER ADMINISTRATION OF THE FIRST DOSE OF OKT3

The effects of the administration of OKT3, a second immunoglobulin G2a (IgG2a) anti-CD3 monoclonal antibody (mAb), and its isotype switch va riant IgA on granulocyte kinetics were compared for 5 hours after the first administration of the mAb, In addition, in vivo and in vitro stu dies were performed on alterations in expression of CD11b and CD62L in duced by these mAbs. Within 15 minutes after administration, OKT3 and IgG2a anti-CD3 mAbs induced a significant decrease in circulating gran ulocytes, whereas IgA anti-CD3 mAb did not. Apparently the initial dec rease in circulating granulocytes depends on the heavy chain of the ad ministered anti-CD3 mAb, resulting in immunocytoadherence and sequestr ation in the lungs, Increased adherence to pulmonary endothelium by al tered expression of CD11b and CD62L plays a minor role in this first g ranulocytopenia, because each mAb exerted the same effects on these ad hesion molecules in vitro. The second decrease in granulocyte counts o ccurred 60 minutes after administration of each mAb and correlated wit h a significant increase in expression of CD 11b and CD62L in vivo and with upregulation of CD11b and down-regulation of CD62L in vitro. The se alterations could be related to the presence of tumor necrosis fact or-alpha both in vivo and in vitro. Thus granulocyte kinetics from 30 minutes after administration of each anti-CD3 mAb resemble neutrophil kinetics induced by TNF-alpha.