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Contribution of T Cell Subsets to Joint Degradation
Arthritis Research & Therapy volume 1, Article number: S06 (1999)
The role of T cells in the pathogenesis of rheumatoid arthritis (RA) has been and remains a matter of debate. One of the arguments for discussing such contribution has been the difficulty to measure the production of cytokines described as characteristic of T cells such as IFNγ . However, when the technology used to raise antigen specific T cell clones was applied to T cells from RA synovium, such cells were found to be fully able to produce IFNγ . In addition, RA synovium immunostaining revealed the presence of IFNγ producing cells. Conversely, the production of IL-4, another T cell cytokine, was found to be low and, to some extent, defective. Such findings led to the classification of RA as a Th1-associated disease. More recently, IL-17 has been described as a proinflammatory cytokine specifically produced by T cells. Studies with supernatants of RA synovium explants showed a high production of bioactive IL-17. Such an effect was linked to a synergistic interaction between IL-17 and the major monocyte-derived cytokines IL-1 and TNFα. Similarly, staining of RA synovium showed the presence of IL-17-producing T cells. Extension of studies with T cell clones from RA synovium indicated that a subset of IFNγ, but not of IL-4-producing T cells, was able to produce IL-17, allowing the classification of IL-17 as a Th1 cytokine.
The addition of blocking anti-IL-17 antibody to culture supernatants was able to reduce by approximately 50% the production of IL-6 LIF as well as that of MMP-1. Such an effect resulted in an important decrease of extracellular matrix destruction when IL-17 was inhibited. Conversely, when the anti-inflammatory cytokines IL-4, IL-13, and, to a lesser extent, IL-10 were added, production of proinflammatory cytokines was inhibited, including that of IL-17. Similarly, this resulted in an increase of TIMP production associated with reduced destruction. In the same conditions, increased repair as indicated by collagen synthesis was observed.
Through their production of cytokines, a subset of Th1 T cells can aggravate the proinflammatory and destructive pattern associated with monocyte activation. Manipulation of the cytokine profile of such a subset may control the destructive pattern, which remains a therapeutic target difficult to control.
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Miossec, P. Contribution of T Cell Subsets to Joint Degradation. Arthritis Res Ther 1, S06 (1999) doi:10.1186/ar20
- Rheumatoid Arthritis
- Proinflammatory Cytokine
- Cell Clone
- Collagen Synthesis
- Rheumatoid Arthritis Synovium