Effector function of type II collagen–stimulated T cells from rheumatoid arthritis patients: Cross‐talk between T cells and synovial fibroblasts

Wiley - Tập 50 Số 3 - Trang 776-784 - 2004
Mi‐La Cho1, Chong-Hyeon Yoon2, Sue‐Yun Hwang2, Mi Kyung Park2, So‐Youn Min1, Sang-Heon Lee2, Sung‐Hwan Park2, Ho‐Youn Kim2
1Catholic Research Institutes of Medical Sciences, The Catholic University of Korea, Seoul, South Korea
2Catholic University of Korea

Tóm tắt

AbstractObjectiveTo 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.MethodsWe used enzyme‐linked immunosorbent assays to measure the levels of interleukin‐15 (IL‐15), tumor necrosis factor α (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.ResultsThe 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.ConclusionThrough 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.

Từ khóa


Tài liệu tham khảo

10.1093/oxfordjournals.rheumatology.a031491

10.1146/annurev.iy.02.040184.001215

10.1002/anr.1780320906

10.1073/pnas.86.2.636

10.1002/art.1780391015

10.1002/1529-0131(199910)42:10<2085::AID-ANR8>3.0.CO;2-Z

He X, 2000, Accumulation of T‐cells reactive to type II collagen in synovial fluid of patients with rheumatoid arthritis, J Rheumatol, 27, 589

10.1002/1529-0131(200103)44:3<561::AID-ANR104>3.0.CO;2-Z

10.1186/ar115

10.4049/jimmunol.166.4.2270

10.1002/1529-0131(200201)46:1<31::AID-ART10029>3.0.CO;2-5

10.1002/art.1780310302

10.1111/j.1600-065X.1992.tb01406.x

Bouaboula M, 1992, Standardization of mRNA titration using a polymerase chain reaction method involving co‐amplification with a multispecific internal control, J Biol Chem, 267, 21830, 10.1016/S0021-9258(19)36687-6

10.1046/j.1523-1747.2001.00239.x

Musso T, 1999, Human monocytes constitutively express membrane‐bound, biologically active, and interferon‐gamma‐upregulated interleukin‐15, Blood, 93, 3531, 10.1182/blood.V93.10.3531.410k32_3531_3539

10.4049/jimmunol.164.5.2832

10.1002/art.10816

Dayer J‐M, 2002, Interleukin 1 or tumor necrosis factor‐α: which is the real target in rheumatoid arthritis?, J Rheumatol, 29, 10

Arend WP, 2002, The mode of action of cytokine inhibitors, J Rheumatol, 29, 16

10.1002/1529-0131(200201)46:1<42::AID-ART10026>3.0.CO;2-A

10.1002/art.1780390205

Thông tin
Thông tin xuất bản

Wiley

Tập 50 Số 3

776-784

Thông tin tác giả