Expression of T cell cytokines in the inflamed synovium from patients with rheumatoid arthritis

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The inflamed synovium of rheumatoid arthritis (RA) is characterized by massive infiltration of CD4+ T cells. It has recently been indicated that the IFN-γ-dominant Th1-type immune response is involved in the disease process of RA. The cytokine profile of CD4+ T cells infiltrates was compared with that of peripheral blood CD4+ CD45+ T cells in patients with RA by intracellular cytokine staining and flow cytometric analysis. We found that synovial tissue CD4+ T cells contained more Th1-type (IFN-γ) and Th0 type (IFN-γ+IL-4) cells, and that there were unique CD4+ T cells such as those producing both IFN-γ and IL-10/IL-13.We also found that fibroblast cell lines from RA synovial tissues spontaneously produced the IL-2-like cytokines Il7 and IL-15, which was augmented by stimulation with IL-1 and TNF-α. IL-15 was able to stimulate the proliferation of synovial tissue T cells more potently than IL-2.Furthermore, the IFN-γ-inducing factor, IL-18, was strongly expressed in the inflammatory joint of RA. Although IL-18 had only minute effect, the level of IFN-γ produced by RA synovial tissues with IL-12 was significantly increased by IL-18, but over 50% reduced by the presence of anti-IL-18.Taken together, our data support that the immune inflammatory response in RA is mediated predominantly by Th1 cells. Il-15, produced by macrophages and synovial fibroblasts, appears to be the important stimulating factor for T cells. Local IFN-γ production may be regulated primarily by IL-12 and readily augmented by the abundance of IL-18 in RA joints.