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