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AB0120 Il-2 therapy results in intrarenal foxp3+ regulatory t cells expansion and decreased number of infiltrating cd4+ t cells in nzb/w mice
  1. A. Rose1,2,
  2. C. von Spee-Mayer1,2,
  3. J. Humrich1,2,
  4. G. Riemekasten1,2
  1. 1German Rheumatism Research Center (DRFZ)
  2. 2Rheumatology And Clinical Immunology, Charité Berlin, 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 (Tcon). Humrich et al. (2010) demonstrated that the IL-2 deficiency in diseased (NZBxNZW) 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.

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 (NZBxNZW) 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 (NZBxNZW) F1 mice treated over a short term with IL-2 showed an enhanced proliferation of Foxp3+ T cells and increased numbers and frequency of CD4+Foxp3+ T cells compared to untreated control mice. On the other hand, long term IL-2 treatment did not result in a persistent expansion of the intrarenal CD4+Foxp3+ T cell population. Nevertheless, total numbers of kidney infiltrating CD4+ T cells were diminished and the conventional T cells (Tcon) 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.

References Humrich, JY et al, PNAS, 2010

Disclosure of Interest None Declared

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