Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases

Front Immunol. 2021 Apr 1;12:648408. doi: 10.3389/fimmu.2021.648408. eCollection 2021.


Regulatory T cells (Treg) are crucial for the maintenance of peripheral tolerance and for the control of ongoing inflammation and autoimmunity. The cytokine interleukin-2 (IL-2) is essentially required for the growth and survival of Treg in the peripheral lymphatic tissues and thus plays a vital role in the biology of Treg. Most autoimmune and rheumatic diseases exhibit disturbances in Treg biology either at a numerical or functional level resulting in an imbalance between protective and pathogenic immune cells. In addition, in some autoimmune diseases, a relative deficiency of IL-2 develops during disease pathogenesis leading to a disturbance of Treg homeostasis, which further amplifies the vicious cycle of tolerance breach and chronic inflammation. Low-dose IL-2 therapy aims either to compensate for this IL-2 deficiency to restore a physiological state or to strengthen the Treg population in order to be more effective in counter-regulating inflammation while avoiding global immunosuppression. Here we highlight key findings and summarize recent advances in the clinical translation of low-dose IL-2 therapy for the treatment of autoimmune and rheumatic diseases.

Keywords: autoimmunity; immune regulation; immune tolerance; immunotherapy; inflammation; interleukin-2; regulatory T cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / therapy*
  • Humans
  • Immune Tolerance
  • Immunotherapy / methods*
  • Interleukin-2 / administration & dosage*
  • Interleukin-2 / adverse effects
  • Interleukin-2 / deficiency
  • Interleukin-2 / immunology
  • Mice
  • Rheumatic Diseases / immunology*
  • Rheumatic Diseases / therapy*
  • T-Lymphocytes, Regulatory / immunology*
  • Treatment Outcome


  • Interleukin-2