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AB0169 IL-2 Therapy Decreases Total Number of Kidney Infiltrating CD4+ T Cells and Reduces the Cellular Activity of CD4+ Effector T Cells in NZB/W Mice
  1. A. Rose1,2,
  2. C. von Spee-Mayer1,2,
  3. L. Kloke3,
  4. J. Humrich1,2,
  5. G. Riemekasten1,2
  1. 1Rheumatology and Clinical Immunology, University Hospital Charité
  2. 2German Rheumatism Research Center (DRFZ)
  3. 3Medizinische Biotechnologie TU Berlin, Berlin, Germany


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). We recently demonstrated that Treg homeostasis in lymphoid organs of diseased (NZBxNZW) F1 mice can be restored by treatment with recombinant IL-2 (IL-2) resulting in an amelioration of kidney disease.

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

Methods (NZBxNZW) F1 mice with active nephritis were treated with recombinant IL-2 either for a short period of 5 days or for a longer period of 30 days in total. Absolute numbers, phenotype and proliferation of kidney infiltrating CD4+ T cell subsets were determined by flow cytometry at different time points.

Results Short-term IL-2 treatment resulted in an enhanced cellular activity and frequencies of intrarenal CD4+Foxp3+ Treg compared to untreated age-matched control mice. Furthermore, long-term IL-2 treatment significantly reduced total numbers of kidney-infiltrating CD4+ T cells (p=0,027) and reduced the frequency of intrarenal Foxp3+ Treg (p=0,002). Furthermore, CD4+ Tcon with a memory/effector phenotype showed markedly reduced signs of cellular activation.

Conclusions Our data indicate 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 frequency of kidney-infiltrating memory/effector T cells and reduces cellular hyperactivity of Tcon, suggesting that Treg suppress the activation and expansion of kidney-infiltrating Tcon. These results may in part explain the amelioration of disease 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 important rationales for an IL-2 based immunotherapy of human disease.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.5582

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