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Ann Rheum Dis 69:1511-1518 doi:10.1136/ard.2009.123422
  • Basic and translational research
  • Extended report

Regulatory T cells control the transition from acute into chronic inflammation in glucose-6-phosphate isomerase-induced arthritis

  1. Thomas Kamradt1
  1. 1Institut für Immunologie, Universitätsklinikum Jena, Leutragraben, Germany
  2. 2Institut für Pathologie, Charité Universitätsmedizin Berlin, Berlin, Germany
  3. 3Novosom AG, Weinbergstraße, Halle, Germany
  1. Correspondence to Thomas Kamradt, Institut für Immunologie, Klinikum der Friedrich-Schiller-Universität Jena, Jena 07740, Germany; immunologie{at}mti.uni-jena.de
  • Accepted 3 January 2010
  • Published Online First 24 May 2010

Abstract

Objectives Glucose-6-phosphate isomerase (G6PI)-induced arthritis is a spontaneously remitting experimental arthritis model. It was hypothesised that regulatory T cells (Tregs) are involved in remission and their role in G6PI-induced arthritis was investigated.

Methods Tregs were depleted by injection of anti-CD25 before immunisation of DBA/1 mice with G6PI. The severity of arthritis was assessed clinically and histologically and the number and function of G6PI-specific T helper (Th) cells were determined by flow cytometry. Th cells and monocytes/macrophages were depleted using anti-CD4 or clodronate-containing liposomes.

Results Injection of anti-CD25 depleted Tregs transiently. Normal numbers of Tregs were restored 5 weeks after G6PI immunisation. Whereas arthritis started to resolve in control mice 3 weeks after immunisation with G6PI, severe arthritis was still present in the anti-CD25-treated mice 12 weeks after immunisation. The most striking ex vivo correlate of non-remitting arthritis was a strong increase in G6PI-specific Th cells 3 days after G6PI immunisation. This difference between treated and control mice declined at later time points. Depletion of CD4 cells ameliorated arthritis in controls but not in anti-CD25-treated mice. In contrast, clodronate-containing liposomes were an effective treatment in both groups.

Conclusions Tregs control the transition from acute self-limiting to non-remitting destructive G6PI-induced arthritis already in the preclinical disease stage. Once established, non-remitting destructive arthritis is not controlled by restoration of normal Treg numbers. These findings question the rationale of therapeutic approaches augmenting Treg number or function in established arthritis.

Footnotes

  • Funding This work was supported by the Interdisciplinary Center for Clinical Research (IZKF) Jena by grants TP 2.13 (to TK) and S4 (to OF), by Deutsche Forschungsgemeinschaft (Br-1372/9-1 to OF and Ka-755/5-1 to TK) and ENDO-Stiftung – Stiftung des Gemeinnützigen Vereins ENDO-Klinik eV to LM.

  • Competing interests None.

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