title: Interleukin-2: Biology, Design and Application.
abstract: Interleukin-2 (IL-2) exerts crucial functions during immune homeostasis via its effects on regulatory T (Treg) cells, and the optimizing and fine-tuning of effector lymphocyte responses. Thus, somewhat paradoxically, low doses of recombinant IL-2 have been used for Treg cell-based immunosuppressive strategies against immune pathologies, while high-dose IL-2 has shown some success in stimulating anti-tumor immune responses. Recent studies of the functional, biophysical and structural characteristics of IL-2 have led to the generation of IL-2 formulations, including IL-2/mAb complexes and IL-2 variants (muteins) that selectively enhance IL-2's immune stimulatory versus inhibitory properties. Here, we review these findings, placing new mechanistic insights into improved next-generation IL-2 formulations within the broader context of IL-2 biology. We conclude by integrating these findings into a framework for understanding IL-2-mediated selective immune modulation.
authors.affiliation: Department of Immunology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Arenas-Ramirez
authors.affiliation: Department of Immunology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Janine
authors.initials: J
authors.lastname: Woytschak
authors.affiliation: Department of Immunology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland. Electronic address: onur.boyman@uzh.ch.
authors.forename: Onur
authors.initials: O
authors.lastname: Boyman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D008969:Molecular Sequence Data; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D007376:Interleukin-2