title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75235-8884, USA.
authors.forename: H
authors.initials: H
authors.lastname: Schulze-Koops
authors.forename: L S
authors.initials: LS
authors.lastname: Davis
authors.forename: T P
authors.initials: TP
authors.lastname: Haverty
authors.forename: M C
authors.initials: MC
authors.lastname: Wacholtz
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000503:physiopathology / Q000628:therapy*; D002097:C-Reactive Protein / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D008934:Mitogens / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007376:Interleukin-2; D008934:Mitogens; C079851:OKT4A monoclonal antibody; D012333:RNA, Messenger; D007371:Interferon-gamma; D002097:C-Reactive Protein