New Molecular and Cellular Mechanisms of Tolerance: Tolerogenic Actions of IL-2

Methods Mol Biol. 2016:1371:11-28. doi: 10.1007/978-1-4939-3139-2_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.

Keywords: Autoimmunity; Immune tolerance; Immunotherapy; Interleukin-2; Regulatory T cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / therapy
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / therapy
  • Humans
  • Immune Tolerance*
  • Immunomodulation
  • Immunotherapy
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / therapy
  • Interleukin-2 / metabolism
  • Interleukin-2 / therapeutic use
  • Mice
  • Receptors, Interleukin-2 / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*

Substances

  • Interleukin-2
  • Receptors, Interleukin-2