Article Text

other Versions

PDF
Imbalance in distribution of functional autologous regulatory T cells in rheumatoid arthritis
  1. Frank Behrens (frank.behrens{at}kgu.de)
  1. Centre for Rheumatic Diseases/ZAFES, J.W. Goethe University, Germany
    1. Andrea Himsel (andrea.himsel{at}kgu.de)
    1. Centre for Rheumatic Diseases/ZAFES, J.W. Goethe University, Germany
      1. Stefan Rehart (s.rehart{at}friedrichsheim.de)
      1. Stiftung Friedrichsheim, Germany
        1. Joanna Stanczyk (joanna.stanczyk{at}usz.ch)
        1. Zentrum für experimentelle Rheumatologie Universitätsspital Zürich, Switzerland
          1. Björn Beutel (bjoern_beutel{at}web.de)
          1. pharmazentrum frankfurt / ZAFES, J.W. Goethe University, Frankfurt/Main, Germany
            1. Stefanie Y Zimmermann (stefanie.zimmermann{at}kgu.de)
            1. Pädiatrische Hämatologie und Onkologie der Universitätsklinik, Germany
              1. Ulrike Koehl (koehl{at}em.uni-frankfurt.de)
              1. Pädiatrische Hämatologie und Onkologie der Universitätsklinik, Germany
                1. Burkhard Möller (burkhard.moeller{at}insel.ch)
                1. Department for Rheumatology, Clinical Immunology, Switzerland
                  1. Steffen Gay (steffen.gay{at}usz.ch)
                  1. Zentrum für experimentelle Rheumatologie Universitätsspital Zürich, Switzerland
                    1. Joachim P Kaltwasser
                    1. Centre for Rheumatic Diseases/ZAFES, J.W. Goethe University, Germany
                      1. Josef M Pfeilschifter (pfeilschifter{at}em.uni-frankfurt.de)
                      1. pharmazentrum frankfurt / ZAFES, J.W. Goethe University, Frankfurt/Main, Germany
                        1. Heinfried H Radeke (radeke{at}em.uni-frankfurt.de)
                        1. Clinic of the JW Goethe University, Germany

                          Abstract

                          Objectives: Regulatory T cells exert their anti- inflammatory activity predominantly by cell contact dependent mechanisms. This led us to investigate the regulatory capacity of autologous peripheral blood (PB) Treg in contact to synovial tissue (ST) cell cultures (STC), and to evaluate their presence in PB, ST, and synovial fluid (SF) of RA patients.

                          Methods: 44 RA and 5 osteoarthritis patients were included in this study. The frequency of IFN-γ secreting cells was quantified in STC, CD3 depleted STC, STC co-cultured with autologous CD4+, and with CD4+CD25+ PB T cells by ELISPOT. Total CD3+, Th1 polarised, and regulatory T cells were quantified by real-time PCR for CD3∊, T-bet, and FoxP3 mRNA, and by immunohistochemistry for FoxP3 protein.

                          Results: RA STC exhibited spontaneous expression of IFN-γ, which was abrogated by depletion of CD3+ T-cells, and specifically reduced by co-culture with autologous PB Treg. The presence of Treg in RA synovitis was indicated by Foxp3 mRNA expression and confirmed by immunohistochemistry. The amount of Foxp3 transcripts however was lower in synovial membrane than in PB and SF. The Tbet/Foxp3 ratio correlated with both, higher grade of ST lymphocyte infiltration and higher disease activity (DAS).

                          Conclusion: Thus, for the first time in human RA we determined the efficacy of autologous Tregs to reduce inflammatory activíty of STC ex vivo, while in synovium FoxP3+ Tregs of RA patients are reduced compared to PB and SF. This local imbalance of Th1 and Treg may be responsible for repetitive rheumatic flares and thus qualify as a target for future therapies.

                          • FoxP3
                          • T-bet
                          • Treg
                          • interferon-gamma
                          • synovial

                          Statistics from Altmetric.com

                          Request permissions

                          If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.