TY - JOUR
T1 - Effector Function of Type II Collagen-Stimulated T Cells from Rheumatoid Arthritis Patients
T2 - Cross-Talk between T Cells and Synovial Fibroblasts
AU - Cho, Mi La
AU - Yoon, Chong Hyeon
AU - Hwang, Sue Yun
AU - Park, Mi Kyung
AU - Min, So Youn
AU - Lee, Sang Heon
AU - Park, Sung Hwan
AU - Kim, Ho Youn
PY - 2004/3
Y1 - 2004/3
N2 - 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.
AB - 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.
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U2 - 10.1002/art.20106
DO - 10.1002/art.20106
M3 - Article
C2 - 15022319
AN - SCOPUS:1542343980
SN - 0004-3591
VL - 50
SP - 776
EP - 784
JO - Arthritis and rheumatism
JF - Arthritis and rheumatism
IS - 3
ER -