Contribution of T Cell Subsets to Joint Degradation

  • Pierre Miossec1

    Affiliated with

    Arthritis Res19991(Suppl 1):S06

    DOI: 10.1186/ar20

    Published: 15 November 1999

    Full text

    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.

    Authors’ Affiliations

    Hospital E Herriot


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