Heterogeneity and Homogeneity in Treg responses to Interleukin-2 [RNAseq2: Differential activation of Immune cell types by IL2-Immunocytokines]

IL2 is an immune-regulatory cytokine that activates both effector and T regulatory cells—a dual function leveraged in immunotherapy. However, pure IL2 induces both activation and suppression, and requires toxic doses due to its short half-life. To address this, the Spangler Lab at Johns Hopkins developed IL2 immunocytokines (IL2-ICs)—antibody-conjugated IL2 fusion proteins targeting IL2Ra (Tregs) or IL2Rb (effector cells), with extended serum half-life. We tested IL2-ICs in Foxp3IRES-GFP mice, harvesting cells at 4, 24, and 64 hours post-injection for bulk RNA-seq. Transcriptomic analysis showed IL2-ICs induced sustained IL2 responses with partial cell-type bias.