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.
Copyright © 2013 Elsevier Inc. All rights reserved.