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SAT0072 Frequency of interferon-gamma-positive TH17 (TH17-1) cells is up-regulated in synovial fluids in patients with rheumatoid arthritis
  1. N. Sakurai,
  2. I. Hidekazu,
  3. K. Kayakabe,
  4. T. Sakairi,
  5. Y. Kaneko,
  6. A. Maeshima,
  7. K. Hiromura,
  8. Y. Nojima
  1. Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan

Abstract

Background Th17 cells are a recently identified CD4+ CD45RO+helper T cell subset that produce IL-17 with proinflammatory actions and are thought to play a critical role in the pathogenesis of collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis (RA) (1). Recently, Nistala et al. showed that Th17 cells obtained from the synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients co-expressed IFN-γ (2). Moreover, they found that Th17-1 cells (Th17 cells co-expressing IFN-γ) were enriched in SF compared to peripheral blood mononuclear cells (PBMC) in patients with JIA. However Th17-1 has not been investigated in patients with RA.

Objectives To explore the significance of Th17-1 in human RA, we examined the frequency of Th1, Th17, and Th17-1 cells in PBMC and SF derived from RA patients by flow cytometry and compared them with those in PBMC from healthy donors.

Methods PBMC from 14 healthy donors (Control-PBMC) and 33 RA patients (RA-PBMC), and SF from 17 RA patients (RA-SF) were obtained and used in this experiment. Isolated mononuclear cells were stimulated with PMA and ionomycin for 5 hours, and then the expression of intracellular cytokines and cell surface markers were analyzed by flow cytometry. Among double positive cells for CD4 and CD45RO, single positive cells for IFN-γ or IL-17, and double positive cells for both IFN-γ and IL-17 were defined as Th1, Th17, and Th17-1 cells, respectively.

Results The frequency of Th17 and Th17-1 cells in PBMC from RA patients were significantly lower than those from controls, whereas the frequency of Th1 cells were similar between them (Th17, 2.2±1.1% vs. 3.0±1.1%, P=0.006; Th17-1, 0.4±0.3% vs. 1.0±0.5%, P=0.0002; Th1, 24±11% vs. 28±5.6%, P=0.0624; RA-PBMC vs. Control-PBMC). Among RA patients, the frequency of Th17 cells in SF was significantly lower than that of PBMC, whereas Th1 and Th17-1 cells in SF were significantly higher than those in PBMC (Th17, 2.2±1.1% vs. 1.8±1.4%, P=0.0381; Th1, 24±11% vs. 38±14%, P=0.0004; Th17-1, 0.4±0.3% vs. 1.1±0.9%, P=0.0006; RA-PBMC vs. RA-SF).

Conclusions In patients with RA, the frequency of both Th1 and Th17-1 cells but not of Th17 in SF were significantly up-regulated, suggesting that a local inflammation in RA joints is dominantly mediated by IFN-γ.

  1. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009. 27:485–517.

  2. Nistala K, Adams S, Cambrook H, Ursu S, Olivito B, de Jager W, Evans JG, Cimaz R, Bajaj-Elliott M, Wedderburn LR. Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment. Proc Natl Acad Sci U S A. 2010. Aug 17;107(33):14751-6.

Disclosure of Interest None Declared

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