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T cell contact-mediated induction of tumor necrosis factor alpha in peripheral blood monocytes is inhibited by autologous serum in rheumatoid arthritis
Arthritis Res Ther volume 5, Article number: 120 (2003)
Background and objective
Cell contact of monocytes with preactivated T cells is one of the strongest known stimuli of monocytic cytokine production and has been implied in the pathogenesis of rheumatoid arthritis (RA). T cells from the synovial membrane of RA patients have been found to induce high levels of tumor necrosis factor alpha (TNF-α) production in synovial macrophages, and monocytes from healthy individuals react similarly to preactivated T cells. The response of peripheral monocytes from RA patients to T-cell contact, however, has not been analyzed previously, and was therefore investigated in the study presented here.
Peripheral blood monocytes from 20 patients with RA and from age-matched healthy donors were isolated by immunomagnetic separation and used in a coculture system with T lymphocytes from unrelated donors. T cells were stimulated with immobilized CD3 and CD28 antibodies, subsequently fixed with glutaraldehyde, and then used in the coculture system at a T cell:monocyte ratio of 7:1. In control experiments, unstimulated fixed T cells or lipopolysaccharide were used.
Lipopolysaccharide-induced TNF-α production of monocytes from RA patients did not differ from the controls. Upon coincubation with preactivated T cells, however, monocytes from RA patients produced significantly lower amounts of TNF-α. This difference was independent of previous or current disease-modifying antirheumatic drug therapy, since it was also found in patients with recent onset RA who had not received immunosuppressive therapy prior to study inclusion. Serum transfer experiments showed the presence of inhibitory factors in sera from RA patients to be one mechanism contributing to the diminished response of RA monocytes, since those sera were also able to inhibit T-cell-dependent TNF-α production in healthy monocytes.
The suppressed response of peripheral blood monocytes from RA patients to preactivated T cells shows that they are not likely to contribute significantly to the excessive levels of TNF-α that are associated with this disease. The inhibitory activity of sera from RA patients in the cell contact-dependent system suggests a counter-regulatory mechanism in the systemic circulation that prevents excessive activation of circulating monocytes in this disease.
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Wagner, U., Rossol, M., Kaltenhäuser, S. et al. T cell contact-mediated induction of tumor necrosis factor alpha in peripheral blood monocytes is inhibited by autologous serum in rheumatoid arthritis. Arthritis Res Ther 5, 120 (2003) doi:10.1186/ar921
- Rheumatoid Arthritis
- Rheumatoid Arthritis Patient
- Coculture System
- Peripheral Blood Monocyte
- Immunomagnetic Separation