Article
IL-2 therapy reduces total number of kidney infiltrating CD4+ T cells and suppresses the cellular activity of intrarenal CD4+ effector T cells in murine lupusnephritis
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Published: | September 12, 2014 |
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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. 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 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: Short term IL-2 treated (NZBxNZW) F1 mice showed an enhanced proliferation of peripheral Foxp3+ Treg and increased frequency of intrarenal CD4+Foxp3+ Treg compared to untreated treated control mice. 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 with a memory/effector were diminished and the cellular activity of intrarenal CD4+ T con was markedly reduced.
Conclusion: 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 and reduces the cellular hyperactivity of Tcon. These results may in part explain the delay of disease progression induced by IL-2 treatment 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.