IL-2 therapy in type 1 diabetes: "Trials" and tribulations

Clin Immunol. 2013 Dec;149(3):324-31. doi: 10.1016/j.clim.2013.02.005. Epub 2013 Feb 22.


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.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmunity
  • Cell Proliferation / drug effects
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Immune Tolerance / drug effects
  • Interleukin-2 / therapeutic use*
  • Mice
  • Receptors, Interleukin-2 / immunology
  • Signal Transduction
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology


  • Hypoglycemic Agents
  • Interleukin-2
  • Receptors, Interleukin-2