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Unmasking of autoreactive CD4 T cells by depletion of CD25 regulatory T cells in systemic lupus erythematosus
  1. Jan Broder Engler1,
  2. Reinmar Undeutsch1,
  3. Lutz Kloke1,
  4. Stefan Rosenberger1,
  5. Marina Backhaus1,
  6. Udo Schneider1,
  7. Karl Egerer1,
  8. Duska Dragun2,
  9. Jörg Hofmann3,
  10. Dörte Huscher1,4,
  11. Gerd-Rüdiger Burmester1,
  12. Jens Y Humrich1,
  13. Philipp Enghard2,
  14. Gabriela Riemekasten1
  1. 1Department of Rheumatology and Clinical Immunology, University Hospital Charité, Berlin, Germany
  2. 2Clinic for Nephrology and Intensive Care Medicine, University Hospital Charité, Berlin, Germany
  3. 3Institute of Virology, University Hospital Charité, Berlin, Germany
  4. 4Department of Epidemiology, German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany
  1. Correspondence to Professor Gabriela Riemekasten, Klinik für Rheumatologie und Klinische Immunologie, Charité Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany; gabriela.riemekasten{at}charite.de

Abstract

Objective Autoreactive CD4 T cells specific for nuclear peptide antigens play an important role in tolerance breakdown during the course of systemic lupus erythematosus (SLE). However, reliable detection of these cells is limited due to their low frequency in peripheral blood. The authors assess autoreactive CD4 T cells in a representative SLE collective (n=38) by flow cytometry and study the influence of regulatory T cells (Treg) on their antigenic challenge.

Methods CD4 T-cell responses were determined according to intracellular CD154 expression induced after 6-h short-term in-vitro stimulation with the SLE-associated autoantigen SmD1(83-119). To clarify the influence of Treg on the activation of autoreactive CD4 T cells, CD25 Treg were depleted by magnetic activated cell sorting before antigen-specific stimulation in selected experiments.

Results In the presence of Treg, autoreactive CD4 T-cell responses to SmD1(83-119) were hardly observable. However, Treg removal significantly increased the frequency of detectable SmD1(83-119)-specific CD4 T cells in SLE patients but not in healthy individuals. Consequently, by depleting Treg the percentage of SmD1(83-119)-reactive SLE patients increased from 18.2% to 63.6%. This unmasked autoreactivity of CD4 T cells correlated with the disease activity as determined by the SLE disease activity index (p=0.005*, r=0.779).

Conclusions These data highlight the pivotal role of the balance between autoreactive CD4 T cells and CD25 Treg in the dynamic course of human SLE. Analysing CD154 expression in combination with a depletion of CD25 Treg, as shown here, may be of further use in approaching autoantigen-specific CD4 T cells in SLE and other autoimmune diseases.

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Footnotes

  • P- E- and G- R- contributed equally to the study.

  • Funding This work was supported by the Deutsche Forschungsgemeinschaft (SFB 650) and grants from the University Hospital Charité Berlin.

  • Patient consent We obtained informed consent regarding the blood collection.

  • Ethics approval This study was conducted with the approval of the Human Research Ethics Committee (EA1/098/07).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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