IL-2 mutein with diminished CD25 binding expands regulatory T cells and blocks autoimmunity

Abstract Since its identification, IL-2 has been tested as a therapy for both oncology and autoimmunity it the ability to expand effector T cells NK well regulatory (Tregs). Due toxicity, focus of molecular engineering improve therapeutic properties index. To target CD4+CD25− CD8+CD25− cells, we rationally designed murine human variant bind IL-2Rβγ (IL2Rbg) heterodimer without binding IL-2Rα (IL2Ra CD25). The mutein demonstrated reduced CD25 induce phosphorylation STAT5 in Tregs while maintaining IL-2Rbgc. Despite these results, IL-2-mutein exhibited significant expansion CD25+Foxp3+ cells. demonstrate biological relevance with two different dosing regimens, completely blocked incidence hyperglycemia NOD mouse. These data suggest identified IL-2.mutein is potent anti-inflammatory vivo.