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FOXP3 expression in blood, synovial fluid and synovial tissue during inflammatory arthritis and intra-articular corticosteroid treatment
  1. S Raghavan1,
  2. D Cao1,
  3. M Widhe1,
  4. K Roth1,
  5. J Herrath1,
  6. M Engström1,
  7. G Roncador2,
  8. A H Banham3,
  9. C Trollmo1,
  10. A I Catrina1,
  11. V Malmström1
  1. 1
    Rheumatology Unit, Department of Medicine at Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden
  2. 2
    Monoclonal Antibodies Unit, Biotechnology Programme, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain
  3. 3
    Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
  1. Correspondence to Dr V Malmström, Centre for Molecular Medicine L8:04, Karolinska University Hospital, 171 76 Stockholm, Sweden; vivianne.malmstrom{at}ki.se

Abstract

Objective: To analyse the distribution of FOXP3+CD25+CD4+ regulatory T cells (Treg) in peripheral blood, synovial fluid and tissue of patients with rheumatic disease during relapse and after local treatment.

Methods: FOXP3 expression was assessed by flow cytometry, immunohistochemistry, immunofluorescence and real-time polymerase chain reaction (RT-PCR). The functional suppressive capacity of Treg was analysed after co-culture with effector CD4+CD25− T cells through assessment of proliferation and cytokine secretion.

Results: It was shown that FOXP3 protein and mRNA expression in synovial fluid T cells was not confined solely to CD25bright T cells as seen in blood, but included CD25intermediate and even CD25neg T cells. Indeed, synovial fluid CD25high T cells showed similar suppressive capacity as CD25bright T cells, indicating the presence of functional Treg in T cells with lower intensity of CD25. In synovial tissue, FOXP3+ cells were present in low numbers within T-cell infiltrates and decreased further after intra-articular glucocorticosteroid administration, in parallel with the general reduction in inflammation.

Conclusions: Identification of synovial fluid FOXP3+ Treg with varying intensities of CD25 opens up possibilities for thorough characterisation of this important T-cell subset in the inflammatory compartment. However, only scarce synovial membrane expression of FOXP3 was found even in the absence of overt inflammation, suggesting that the synovial membrane is a site that would benefit therapeutically from Treg expansion.

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Footnotes

  • ▸ Additional figures are published online only at http://ard.bmj.com/content/vol68/issue12

  • TDC, MW, KR and JH contributed equally to the studies.

  • Funding This study was supported by grants from Margareta af Ugglas, Alex and Eva Wallström, Börje Dahlin, Tore Nilsson, Magn. Bergvall, Nanna Svartz’, Åke Wiberg, King Gustaf the V:s 80 year Foundation, Swedish Association against Rheumatism, Swedish Medical Association, Swedish Research Council, an EU FP6 project, AutoCure LSHB CT- 006-018661, 2 and Leukemia Research Fund (Alison Banham).

  • Competing interests AHB and GR receive royalty payments from the licensing of their anti-FOXP3 monoclonal antibodies. The remaining authors declare no competing interests.

  • Ethics approval Approval from the Karolinska University Hospital.

  • This publication reflects only the author’s views; the European Community is not liable for any use that may be made of the information herein.

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