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AB0193 IL-2 therapy in murine lupus nephritis leads to an expansion of intrarenal FOXP3+ regulatory T cells
  1. A. Rose1,2,
  2. J.Y. Humrich1,2,
  3. G. Riemekasten1,2
  1. 1Charité Berlin
  2. 2DRFZ, Berlin, Germany

Abstract

Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an acquired IL-2 deficiency, which leads to a homeostatic imbalance between regulatory T cells (Treg) and effector T cells. Recently, we have shown that compensation of the IL-2 deficiency in diseased lupus mice by treatment with recombinant IL-2 (IL-2) ameliorates already established disease by promoting the homeostatic proliferation of regulatory T cell (Treg) in the lymphoid organs (Humrich et al, PNAS 2010).

Objectives The aim of this study was to investigate the impact of IL-2 therapy on intrarenal Foxp3+ Treg and kidney infiltrating CD4+ T cells in (NZBxNZW) F1 mouse model of lupus nephritis.

Methods Aged-matched (NZBxNZW) F1 mice were treated with recombinant IL-2 either over period of 24h or over a long-term period of 20 days with PBS treated mice as a control group. Phenotyping of intrarenal T cell were done by flow cytometry analyses.

Results Our preliminary data of short term IL-2 treated (NZBxNZW) F1 mice showed an increase in numbers and frequency of CD4+Foxp3+ Tregwithin IL-2 treated mice compared to control mice and also increased the proliferation of FoxP3+ regulatory T cells. However, long-term IL-2 treatment mice over a period of 20 days showed a consistent percentage of CD4+FoxP3+ cells. Also the total numbers of kidney infiltrating CD4+ T cells were reduced during long-term experiment with reduced signs of cellular activation.

Conclusions This preliminary data could show that a supplementary short-term IL-2 treatment expands the number and frequency of the intrarenal Treg pool. On the other hand, long term IL-2 treatment diminishes the numbers of kidney infiltrating CD4+ Tcon and their cellular activity. These results points out the important role of intrarenal Treg for the suppression of kidney disease in lupus mice and may in part explain the delay of disease progression induced by treatment with IL-2 and might give additional rationales for an IL-2 based immunotherapy of human disease.

  1. Humrich, JY et al. (2010). Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proc Natl Acad Sci USA 107, 204-9

Disclosure of Interest None Declared

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