Artikel
Low-dose Interleukin-2 therapy selectively expands regulatory T cells in parallel to reduction of disease activity in two patients with severe refractory SLE
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Autoren
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Caroline von Spee-Mayer
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Elise Siegert
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Angelika Rose
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Dimas Abdirama
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Anika Klaus
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Tobias Alexander
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Gerd-Rüdiger Burmester
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Andreas Radbruch
- Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
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Jens Humrich
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Gabriela Riemekasten
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
| Veröffentlicht: | 12. September 2014 |
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Gliederung
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Background: Systemic lupus erythematosus (SLE) has been associated with quantitative and qualitative aberrations of CD4+ Foxp3+ regulatory T cells (Treg) and with impaired production of Interleukin-2 (IL-2), the essential cytokine for Treg homeostasis. These observations provide a strong rationale for an IL-2-based therapy to selectively expand Treg in order to re-establish tolerance in SLE. In this study we aimed to investigate the effect of low-dose IL-2 (aldesleukin; Proleukin®) on CD4+Foxp3+CD127lo Treg and other lymphocyte subsets in two SLE patients.
Methods: Off-label treatment with subcutaneously administered low-dose aldesleukin was performed after written informed consent of two patients with severe SLE refractory to various other therapies. The patients received four treatment cycles, each consisting of daily injections of 1.5 or 3mio IU aldesleukin on five consecutive days followed by wash-out periods of 9-16 days between the cycles. Peripheral blood lymphocytes were analyzed before and after each treatment cycle by flow cytometry. The clinical response was evaluated by the SLE disease activity score (SLEDAI).
Results: The frequency of peripheral Foxp3+CD127lo Treg cells among CD3+CD4+ T cells increased from approximately 20% at baseline up to 55% during the IL-2 treatment cycles in both patients. Furthermore, the CD25 expression (MFI) was increased up to 6-fold in Treg but not in CD4+Foxp3- conventional T cells (Tcon). Proliferation, evaluated by expression of Ki67, was also strongly and selectively induced in Treg during IL-2 treatment as compared to Tcon. In addition, proliferation and frequencies of CD3-CD56+ NK cells were augmented during IL-2 treatment. These effects on peripheral lymphocytes were accompanied by reduction of the patients' disease activity and a remarkable decrease of anti-dsDNA antibody levels.
Conclusion: These data demonstrate that low-dose IL-2 therapy is effective in selectively expanding Foxp3+CD127loCD25++ Treg in SLE patients in parallel to a reduction of disease activity. The contribution of Treg and other lymphocyte subsets like NK and B cells to the clinical efficacy of low-dose IL-2 will be evaluated in more detail in a recently initiated clinical study with low-dose IL-2 in the treatment of SLE.
