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  • Title: Ligation of CD40 induced tumor necrosis factor-alpha in rheumatoid arthritis: a novel mechanism of activation of synoviocytes.
    Author: Harigai M, Hara M, Nakazawa S, Fukasawa C, Ohta S, Sugiura T, Inoue K, Kashiwazaki S.
    Journal: J Rheumatol; 1999 May; 26(5):1035-43. PubMed ID: 10332965.
    Abstract:
    OBJECTIVE: To determine the immunopathological significance of CD40/CD40 ligand (CD40L) interaction in rheumatoid arthritis (RA). METHODS: The expression of CD40 ligand (CD40L) in synovial tissues (ST) from patients with RA was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) was measured by ELISA. Expression of CD40 on ST cells was quantified by anti-CD40 monoclonal antibodies and 125I labelled anti-mouse IgG. RESULTS: Immunohistochemistry showed CD40L+ T cells in RA ST. Ligation of CD40 on RA ST cells significantly increased the production of TNF-alpha in a dose dependent fashion. Adherent, but not non-adherent, fraction of ST cells responded to ligation of CD40 to produce TNF-alpha. Interferon-gamma (IFN-gamma), interleukin 4 (IL-4), or IL-13 acted synergistically with CD40 ligation to enhance TNF-alpha production by ST cells. IL-10 exerted inhibitory effects on both CD40 ligation induced and CD40 ligation plus IFN-gamma induced TNF-alpha production by ST cells. CONCLUSION: These data indicate activated T cells participate in synovial inflammation of RA via CD40L to stimulate the production of TNF-alpha by ST cells. The effect of CD40 ligation is modulated by the presence of several cytokines, e.g., IFN-gamma, IL-4, IL-10, and IL-13.
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