Differential clinical efficacy of anti-CD4 monoclonal antibodies in rat adjuvant arthritis is paralleled by differential influence on NF-kappaB binding activity and TNF-alpha secretion of T cells.

Abstract

The aim of this study was to analyze the differential effects of three anti-CD4 monoclonal antibodies (mAbs) (with distinct epitope specifities) in the treatment of rat adjuvant arthritis (AA) and on T-cell function and signal transduction. Rat AA was preventively treated by intraperitoneal injection of the anti-CD4 mAbs W3/25, OX35, and RIB5/2 (on days -1, 0, 3, and 6, i.e. 1 day before AA induction, on the day of induction [day 0], and thereafter). The effects on T-cell reactivity in vivo (delayed-type hypersensitivity), ex vivo (ConA-induced proliferation), and in vitro (mixed lymphocyte culture) were assessed. The in vitro effects of anti-CD4 preincubation on T-cell receptor (TCR)/CD3-induced cytokine production and signal transduction were also analyzed. While preventive treatment with OX35 and W3/25 significantly ameliorated AA from the onset, treatment with RIB5/2 even accelerated the onset of AA by approximately 2 days (day 10), and ameliorated the arthritis only in the late phase (day 27). Differential clinical effects at the onset of AA were paralleled by a differential influence of the mAbs on T-cell functions, i.e. in comparison with OX35 and W3/25, the 'accelerating' mAb RIB5/2 failed to increase the delayed-type hypersentivity (DTH) to Mycobacterium tuberculosis, increased the in vitro tumor necrosis factor (TNF)-alpha secretion, and more strongly induced NF-kappaB binding activity after anti-CD4 preincubation and subsequent TCR/CD3-stimulation. Depending on their epitope specificity, different anti-CD4 mAbs differentially influence individual proinflammatory functions of T cells. This fine regulation may explain the differential efficacy in the treatment of AA and may contribute to the understanding of such treatments in other immunopathologies.

• Authors: Dirk Pohlers, Carsten B Schmidt-Weber, Angels Franch, Jürgen Kuhlmann, Rolf Bräuer, Frank Emmrich, Raimund W Kinne
• Journal: Arthritis research (Arthritis Res) Vol. 4 Issue 3 Pg. 184-9 ( 2002) ISSN: 1465-9905 [Print] England
• PMID: 12010568 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• CD4 Antigens
• NF-kappa B
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, pharmacology, therapeutic use)
• Arthritis, Experimental (metabolism, physiopathology, prevention & control, therapy)
• CD4 Antigens (immunology)
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• Disease Models, Animal
• Injections, Intraperitoneal
• Lymphocyte Activation (drug effects)
• NF-kappa B (metabolism)
• Rats
• Signal Transduction
• Tumor Necrosis Factor-alpha (metabolism)