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

Hendrik Schulze-Koops, Laurie S. Davis, Thomas P. Haverty, Mary C. Wacholtz, Peter E. Lipsky

Research output: Contribution to journalArticle

41 Scopus citations

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-χ 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-χ producing Th1 cells.

Original languageEnglish (US)
Pages (from-to)2065-2076
Number of pages12
JournalJournal of Rheumatology
Volume25
Issue number11
StatePublished - Nov 1 1998

Keywords

  • Anti-CD4 monoclonal Antibody
  • Cytokines
  • Mab therapy
  • Reverse transcription-polymerase chain reaction

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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