Volume 13 Supplement 2

Kitasato Symposium 2011: Translational prospects for cytokines in 2011

Open Access

Natural Treg and role of IL-2 in lupus

  • Gabriela Riemekasten1 and
  • Jens Y Humrich1
Arthritis Research & Therapy201113(Suppl 2):O7

DOI: 10.1186/ar3411

Published: 16 September 2011

Background

Effector T cells play an important role in the pathogenesis of lupus. As recently shown in murine lupus, they contribute to tissue damage and glomerulonephritis.

Methods

The role of naturally occurring regulatory T cells (Treg) and of IL-2 was studied in vitro and in vivo by using flow cytometry and the NZB/W lupus mouse model.

Results

In healthy individuals as well as in young lupus prone mice without any signs of the disease, effector T cells are tightly controlled by naturally occurring regulatory T cells (Treg) that can be shown by different approaches: 1. After depletion of Treg cells by anti-CD25 therapy, murine lupus is strongly accelerated. 2. After passive transfer of Treg (CD4+CD25+ T cells consisting of 95% FoxP3+ T cells), murine lupus improved reflected by reduced proteinuria and increased survival compared to control mice [1]. 3. In vitro depletion of Treg lead to better detection of autoantigen-specific effector T cells with frequencies above the detection limit for flow cytometry. The frequency of autoangien-specific T cells correlate with the disease activity in human and murine lupus. The control of effector T cells by Treg cells can be also used for studying the phenotype of effector T cell and their function at an autoantigen-specific level. However; as shown in the murine NZB/W lupus model, there is a progressive loss of Treg/Tcon homeostasis during lupus development in different compartments with a progressive Treg deficiency. In lupus mice with proteinuria, the phenotype of effector T cells is very similar to the T cell phenotype obtained in IL-2 deficient mice. As known from the literature, IL-2 levels are decreased in SLE patients. According to the characteristics of Treg, they are more sensitive to IL-2 deficiency. Supporting this, addition of IL-2 resulted in a dominant proliferation of Treg cells. In murine lupus, IL-2 improved survival and decreased proteinuria in diseased NZB/W mice.

Conclusions

Our data support the possible role of Treg and of IL-2 supplementation in lupus therapy. Further studies are underway to evaluate IL-2 supplementation and its effects on immune cells and disease symptoms in lupus.

Authors’ Affiliations

(1)
Department of Rheumatology and Clinical Immunology, Charité University hospital

References

  1. Humrich JY, Morbach H, Undeutsch R, Enghard P, Rosenberger S, Weigert O, Kloke L, Heimann J, Gaber T, Brandenburg S, Scheffold A, Huehn J, Radbruch A, Burmester GR, Riemekasten G: Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proc Natl Acad Sci USA. 2010, 107 (1): 204-209. 10.1073/pnas.0903158107.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© BioMed Central Ltd 2011

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