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A3.12 Intrarenal Foxp3+ Regulatory T Cells Expansion and Decreased Number of Infiltrating CD4+ T Cells in Murine Lupus by IL-2 Therapy
  1. A Rose1,2,
  2. JY Humrich1,2,
  3. G Riemekasten1,2
  1. 1German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin, Germany
  2. 2University Hospital Charité, Rheumatology and Clinical Immunology, Berlin, Germany

Abstract

Background and Objectives Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by an acquired IL-2 deficiency, which leads to a homeostatic imbalance between regulatory T cells (Treg) and effector T cells (Tcon). Humrich et al, (2010) demonstrated that the IL-2 deficiency in diseased (NZB × NZW) F1 mice can be rebalanced in lymphoid organs using a treatment with recombinant IL-2 (IL-2) by promoting the homeostatic proliferation of regulatory T cells. The aim of this study was to investigate the impact of IL-2 therapy on intrarenal Foxp3+ Treg and kidney infiltrating CD4+ cells in (NZB × NZW) F1 mouse model of lupus nephritis.

Materials and Methods (NZB × NZW) F1 mice with active nephritis were treated with recombinant IL-2 either over a short period or for a total of 30 days. Absolute numbers, phenotype and proliferation of kidney infiltrating CD4+ T cells were determined by flow cytometry.

Results (NZB × NZW) F1 mice treated over a short term with IL-2 showed an enhanced proliferation of Foxp3+ Treg and increased numbers and frequency of CD4+Foxp3+ Treg compared to un-treated treated control mice. On the other hand, long term IL-2 treatment did not result in a persistent expansion of the intrarenal Foxp3+ Treg population. Nevertheless, total numbers of kidney infiltrating CD4+ T cells were diminished and the CD4+ T con showed reduced signs of cellular activation.

Conclusions Our data indicates that short term IL-2 treatment is able to expand the size of the intrarenal Treg pool. In contrast, long term IL-2 treatment decreases the numbers of kidney infiltrating CD4+ T cells. These results may in part explain the delay of disease progression induced by treatment with IL-2 and underline the important role of intrarenal Treg for the suppression of kidney disease in lupus mice. These results also provide additional rationales for an IL-2 based immunotherapy of human disease.

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