title: IL-2 therapy in type 1 diabetes: "Trials" and tribulations.
abstract: IL-2 facilitates immunity or tolerance depending on its availability. In model systems, it is well established that low dose IL-2 promotes selective expansion of regulatory T cells (Treg), an IL-2 responsive cell type known to control autoimmunity. Moreover, many autoimmune diseases are marked by defects in Treg and/or IL-2/IL-2 receptor signaling. Thus, patients with immune-mediated diseases were treated with IL-2 with the goal of increasing Treg and controlling autoimmunity. In graft versus host disease, HCV-induced vasculitis and type 1 diabetes (T1D), Treg numbers increased with IL-2 therapy. Yet there was no relationship between Treg number and clinical outcome. In fact, in T1D subjects treated with rapamycin and IL-2 therapy there was no measureable clinical benefit. In this review, we compare results from IL-2 treatment of patients with immune-mediated diseases, discuss possible mechanisms of IL-2 treatment and suggest future directions for use of IL-2 therapy in T1D.
authors.affiliation: Translational Immunology, Benaroya Research Institute, Seattle, WA, USA.
authors.forename: S Alice
authors.initials: SA
authors.lastname: Long
authors.forename: Jane H
authors.initials: JH
authors.lastname: Buckner
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
mesh_terms: D000818:Animals; D015551:Autoimmunity; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007108:Immune Tolerance / Q000187:drug effects; D007376:Interleukin-2 / Q000627:therapeutic use*; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D007004:Hypoglycemic Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2
keywords: Clinical trials;; GVHD; GVHD;; HCV-induced vasculitis; IL-2 receptor; IL-2;; IL2R; MMTT; Regulatory T cells; Regulatory T cells;; T1D; Teff; Treg; Type 1 diabetes;; effector T cells; graft versus host diseases; mixed meal tolerance test; type 1 diabetes