CC-122 induces degradation of Aiolos and Ikaros in primary T cells and increased IL-2 secretion. (A) Primary T cells were pretreated with DMSO or CC-122 (0.001-10 µM) for 1 hour prior to anti-CD3 stimulation. On day 2, supernatants were harvested and assayed for IL-2 expression by ELISA. Data shown are from 3 independent normal donors tested in triplicate (± SEM). (B) Primary T cells were pretreated with DMSO or 1 μM CC-122 for 1 hour prior to anti-CD3 stimulation in the presence or absence of 10 μM MG-132. At indicated time points, cells were harvested, lysates were separated by SDS-PAGE, and levels of Aiolos, Ikaros, and β-actin were assessed. (C) Viably frozen peripheral blood mononuclear cells from baseline cycle 1 day 1 (C1D1) at 0 hours and C1D1 (1.5 and 5 hours postadministration of CC-122) were analyzed by flow cytometry for Aiolos expression in CD3⁺ T cells. MEFL, molecules of equivalent fluorescein. (D) Whole blood drawn from DLBCL patients on C1D1 at 0 hours and 1.5 hours postadministration CC-122 were incubated for 48 hours at 37°C with anti-CD3 antibody. Supernatants were harvested and IL-2 expression was measured by luminex.