Figure 1: High-doses rhIL-2 injection in NOD induce neutralizing anti-rhIL-2 antibodies.

(a–f) Five-to-14-week-old male or female NOD mice were daily treated with PBS or high-doses rhIL-2 (250,000; 500,000 or 1,000,000 IU) over 30 days. (a,b) Kaplan-Meier survival curves of treated female (a, top panel) or male (b, top panel) mice; and diabetes incidence in female (a, bottom panel) or male (b, bottom panel) mice. (c) Percentage of dead, diabetic or alive and non-diabetic NOD mice after 30 days of treatment; IL-2-treated: pool of (250,000; 500,000 and 1,000,000 IU IL-2 treated mice. (d) Percentage of Foxp3⁺ among CD3⁺ CD4⁺ splenocytes of NOD mice treated for 5 to 30 days with high-doses IL-2 or PBS. (e) Serum anti-rhIL-2 IgG titres of untreated B6 mice and pre-diabetic NOD mice treated for 0, 7 or 30 days with high-dose IL-2. (f) Proliferation of CTLL-2 cells cultured for 3 days with 3 IU ml⁻¹ rhIL-2 and serially diluted serum from B6 (closed circles) or NOD mice treated for 30 days with high-dose rhIL-2 (open circles). Proliferation is expressed as percentage of control (CTLL-2 cultured for 3 days with 3 IU ml⁻¹ rhIL-2 without mouse serum). Data are cumulative of at least two independent experiments. ns, not significant. ***P<0.001 (non-parametric Mann-Whitney test).