Interleukin-2 (IL-2) is crucial for the growth and survival of regulatory T cells (Treg) and, thus, for the control of autoimmunity. 1 2 In previous studies, we have proven a causal relationship between an acquired IL-2-deficiency, defects in Treg biology and the development of systemic lupus erythematosus (SLE). 3 Accordingly, we showed that compensation of IL-2 deficiency by IL-2 therapy corrects associated Treg defects and ameliorates already established disease in lupus-prone mice. 3 In line with this, two independent clinical studies showed recently that low-dose IL-2 induced expansion of the Treg pool and reduced clinical symptoms in two different immunological diseases without known IL-2 deficiency. 4 5 These promising clinical findings in conjunction with preclinical data 3 6 7 provide strong rationales for an IL-2-based immunotherapy of SLE in order to restore Treg activity and, thus, to re-establish endogenous mechanisms of tolerance that can counteract autoimmunity. Here we report a rapid and robust reduction of disease activity in parallel with a remarkable expansion of the Treg population by low-dose IL-2 therapy in one patient with a longterm history of SLE and increased disease activity refractory or intolerant to a large variety of approved and experimental therapies, including azathioprine, mycophenolate, rituximab, cyclophosphamide, bortezomib and, lastly, belimumab, in combination with methotrexate. The therapeutic regimen consisted of four treatment cycles each with daily subcutaneous injections of recombinant human IL-2 (aldesleukin) at single doses of 1.5 or 3.0 million international units (only second cycle) on five consecutive days separated by washout periods of 9–16days and followed by a 9-week follow-up period (adapted from Saadoun et al 4). Treatment with hydroxychloroquine and prednisolone was maintained during the whole study. This 36-year-old female patient with SLE had a high disease activity at baseline due to active arthritis (tenderness in 14 joints, morning stiffness of 2 h, recurrent swellings), clinical and laboratory signs of myositis, rash, hypocomplementaemia and elevated anti-dsDNA antibodies (SELENA-SLEDAI 14). Already after the first treatment cycle with IL-2, signs of arthritis and 10 days later, just before the second cycle, active skin eruptions and laboratory signs of myositis also disappeared (figure 1 A–C). Myalgia also improved 3 weeks later. Additionally, serum levels