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

J Rheumatol. 1998 Nov;25(11):2065-76.


Objective: To test the hypothesis that administration of a non-depleting monoclonal antibody (Mab) to CD4 may alter T cell function in patients with rheumatoid arthritis (RA), possibly associated with clinical benefit.

Methods: The patients with RA treated were a subset from a multicenter, placebo-controlled, randomized, double-blind trial and were randomized into one of 2 treatment groups receiving placebo or +/-450 mg of a humanized anti-CD4 Mab (ORTHOCLONE OKTcdr4a) per week for 2 treatment cycles. For the third cycle, patients who had received Mab during 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 production by mitogen-stimulated peripheral blood T cells was monitored, cytokine mRNA levels were assessed in stimulated peripheral blood mononuclear cells (PBMC) by semiquantitative polymerase chain reaction, and clinical activity was also measured during the study.

Results: Administration of the anti-CD4 Mab, but not placebo, was followed by an immediate transient clinical benefit accompanied by a significant decrease in C-reactive protein levels. There was no significant change in the number of circulating CD4+ T cells. However, 7 weeks after the second Mab treatment, interleukin 2 (IL-2) and IFN-gamma mRNA levels were significantly 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 related to a decrease in the function of IL-2 and IFN-gamma producing Th1 cells.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / physiopathology
  • Arthritis, Rheumatoid / therapy*
  • C-Reactive Protein / metabolism
  • CD4 Antigens / immunology*
  • CD4 Lymphocyte Count
  • Double-Blind Method
  • Humans
  • Interferon-gamma / genetics
  • Interleukin-2 / genetics
  • Mitogens / pharmacology
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th1 Cells / drug effects
  • Th1 Cells / metabolism
  • Th1 Cells / physiology*
  • Treatment Outcome


  • Antibodies, Monoclonal
  • CD4 Antigens
  • Interleukin-2
  • Mitogens
  • OKT4A monoclonal antibody
  • RNA, Messenger
  • Interferon-gamma
  • C-Reactive Protein