title: New Molecular and Cellular Mechanisms of Tolerance: Tolerogenic Actions of IL-2.
abstract: Interleukin-2 (IL-2) is an old molecule with brand new functions. Indeed, IL-2 has been first described as a T-cell growth factor but recent data pointed out that its main function in vivo is the maintenance of immune tolerance. Mechanistically, IL-2 is essential for the development and function of CD4(+) Foxp3(+) regulatory T cells (Treg cells) that are essential players in the control of immune responded to self, tumors, microbes and grafts. Treg cells are exquisitely sensitive to IL-2 due to their constitutive expression of the high affinity IL-2 receptor (IL-2R) and the new paradigm suggests that low-doses of IL-2 could selectively boost Treg cells in vivo. Consequently, a growing body of clinical research is aiming at using IL-2 at low doses as a tolerogenic drug to boost endogenous Treg cells in patients suffering from autoimmune or inflammatory conditions. In this manuscript, we briefly review IL-2/IL-2R biology and the role of IL-2 in the development, maintenance, and function of Treg cells; and also its effects on other immune cell populations such as CD4(+) T helper cells and CD8(+) memory T cells. Then, focusing on type 1 diabetes, we review the preclinical studies and clinical trials supporting the use of low-doses IL-2 as a tolerogenic immunotherapy. Finally, we discuss the limitations and future directions for IL-2 based immunotherapy.
authors.affiliation: INSERM U932, 26 rue d'Ulm, 75005, Paris, France. louis.perol@curie.fr.|Institut Curie, Section Recherche, 26 rue d'Ulm, 75005, Paris, France. louis.perol@curie.fr.
authors.forename: Louis
authors.initials: L
authors.lastname: Pérol
authors.affiliation: INSERM U932, 26 rue d'Ulm, 75005, Paris, France.|Institut Curie, Section Recherche, 26 rue d'Ulm, 75005, Paris, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Piaggio
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D007167:Immunotherapy; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D007376:Interleukin-2 / Q000378:metabolism / Q000627:therapeutic use; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2
keywords: Autoimmunity; Immune tolerance; Immunotherapy; Interleukin-2; Regulatory T cells