Down-regulation of lymphocyte CD4 antigen expression by administration of anti-CD4 monoclonal antibody.

Modulation of surface CD4 antigen expression was assessed by flow cytometry after calibration with 125I-labeled anti-CD4 monoclonal antibodies (mAbs). Three patients with severe psoriasis treated with BB14 (anti-CD4 mouse IgG1) and five patients with rheumatoid arthritis treated with BL4 (anti-CD4 mouse IgG2a) were analyzed for sequential changes in surface CD4 expression on CD4+ blood lymphocytes. Anti-CD4 mAb treatment induced a decrease of 50 to 80% of CD4 expression, with slow and partial recovery after cessation of mAb administration. CD4 modulation was related to mAb dosage and mAb concentration in plasma. It was achieved at nonsaturating concentration. In vitro incubation of blood mononuclear cells induced CD4 modulation of similar kinetics and magnitude, associated with decrease of 5-10% of CD3 expression. CD4 modulation required both an intact Fc part of the antibody and the presence of monocytes. The possible role of CD4 modulation should be considered along with other functional activities of anti-CD4 mAbs in analyzing the mechanisms of the clinical effects of these antibodies.