Tolerance, not immunity, crucially depends on IL-2

Nat Rev Immunol. 2004 Sep;4(9):665-74. doi: 10.1038/nri1435.


Interleukin-2 (IL-2) was identified based on its potent T-cell growth-factor activity and is widely considered to be a key cytokine in T-cell-dependent immune responses. However, the main non-redundant activity of this cytokine centres on the regulation of T-cell tolerance, and recent studies indicate that a failure in the production of CD4(+)CD25(+) regulatory T cells is the underlying cause of autoimmunity in the absence of IL-2. In marked contrast to the importance of IL-2 in peripheral T-cell tolerance, T-cell immunity is readily elicited to various agents in the absence of IL-2 in vivo. Here, we discuss these findings and, in particular, the action of IL-2 on regulatory T cells and effector cells, and the targeting of IL-2 and/or the IL-2 receptor in clinical settings.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Division / immunology
  • Cell Division / physiology
  • Cell Survival / immunology
  • Cell Survival / physiology
  • Humans
  • Immune Tolerance / immunology
  • Immune Tolerance / physiology*
  • Immunity / immunology
  • Immunity / physiology*
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism*
  • Signal Transduction / immunology
  • Signal Transduction / physiology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology


  • Interleukin-2