Effector Function of Type II Collagen-Stimulated T Cells from Rheumatoid Arthritis Patients: Cross-Talk between T Cells and Synovial Fibroblasts

Mi La Cho, Chong Hyeon Yoon, Sue Yun Hwang, Mi Kyung Park, So Youn Min, Sang Heon Lee, Sung Hwan Park, Ho Youn Kim

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Objective. To investigate the effector function exerted by type II collagen (CII)-stimulated T cells on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), and to determine their contribution to RA pathogenesis. Methods. We used enzyme-linked immunosorbent assays to measure the levels of interleukin-15 (IL-15), tumor necrosis factor a (TNFα), and IL-18 production by FLS that were cocultured with antigen-activated T cells. Likewise, we analyzed the levels of interferon-γ (IFNγ) and IL-17 production by RA T cells coincubated with FLS. To investigate the cross-talk between CII-stimulated T cells and RA FLS, we examined the effect of using a transwell membrane to separate T cells and FLS in a culture chamber, as well as the effect of adding an antibody to block CD40 ligation. Results. The levels of IL-15, TNFα, IFNγ, and IL-17 were all significantly increased in the serum of RA patients compared with normal control serum. Among the patients, the group with a stronger T cell proliferation response to CII showed higher levels of these inflammatory mediators. When coincubated with RA FLS, these T cells induced the production of IL-15, TNFα, and IL-18 by FLS with an intensity that increased in proportion to the duration of CII stimulation. T cells, in turn, responded to FLS stimulation by secreting higher amounts of IL-17 and IFNγ in coculture. Interestingly, T cells that were activated by CII for longer periods of time showed stronger induction of these cytokines. The cross-talk between T cells and FLS appeared to require direct cell-cell contact as well as CD40, ligation, at least in part. Conclusion. Through repeated stimulation by CII, RA synovial T cells became trained effector cells that induced the production of proinflammatory mediators by FLS, while in the process the T cells becoming more sensitized to the activation signal from FLS.

Original languageEnglish (US)
Pages (from-to)776-784
Number of pages9
JournalArthritis and rheumatism
Volume50
Issue number3
DOIs
StatePublished - Mar 1 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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