REDUCTION OF TH1 CELL-ACTIVITY IN THE PERIPHERAL-CIRCULATION OF PATIENTS WITH RHEUMATOID-ARTHRITIS AFTER TREATMENT WITH A NON-DEPLETING HUMANIZED MONOCLONAL-ANTIBODY TO CD4

Objective. To test the hypothesis that administration of a non-depleti ng monoclonal antibody (Mab) to CD4 may alter T cell function in patie nts with rheumatoid arthritis (RA), possibly associated with clinical benefit. Methods, The patients with RA treated were a subset from a mu lticenter, placebo-controlled, randomized, double-blind trial and were randomized into one of 2 treatment groups receiving placebo or +/- 45 0 mg of a humanized anti-CD4 Mab (ORTHOCLONE OKTcdr4a) per week for 2 treatment cycles. For the third cycle, patients who had received Mab d uring the first 2 courses were given placebo, whereas the patients who were originally given placebo received anti-CD4 Mab. To evaluate the impact of anti-CD4 Mab treatment on T cell functions, cytokine product ion by mitogen stimulated peripheral blood T cells was monitored, cyto kine mRNA levels were assessed in stimulated peripheral blood mononucl ear cells (PBMC) by semiquantitative polymerase chain reaction, and cl inical activity was also measured during the study. Results, Administr ation of the anti-CD4 Mab, but not placebo, was followed by an immedia te transient clinical benefit accompanied by a significant decrease in C-reactive protein levels. There was no significant change in the num ber of circulating CD4+ T cells. However, 7 weeks after the second Mab treatment, interleukin 2 (IL-2) and IFN-gamma mRNA levels were signif icantly reduced in all anti-CD4 Mab treated patients, but neither was reduced in placebo-treated patients. Conclusion. Clinical improvement in patients with RA treated with a non-depleting Mab to CD4 may be rel ated to a decrease in the function of IL-2 and LFN-gamma. producing Th 1 cells.