Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy

Immunity. 2013 Jan 24;38(1):13-25. doi: 10.1016/j.immuni.2013.01.004.

Abstract

Interleukin-2 (IL-2) is a pleiotropic cytokine produced after antigen activation that plays pivotal roles in the immune response. Discovered as a T cell growth factor, IL-2 additionally promotes CD8(+) T cell and natural killer cell cytolytic activity and modulates T cell differentiation programs in response to antigen, promoting naïve CD4(+) T cell differentiation into T helper 1 (Th1) and T helper 2 (Th2) cells while inhibiting T helper 17 (Th17) and T follicular helper (Tfh) cell differentiation. Moreover, IL-2 is essential for the development and maintenance of T regulatory cells and for activation-induced cell death, thereby mediating tolerance and limiting inappropriate immune reactions. In this review, we focus on the molecular mechanisms and complex cellular actions of IL-2, its cooperative and opposing effects with other cytokines, and how both promoting and blocking the actions of IL-2 are being utilized in clinical medicine.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Humans
  • Immune Tolerance*
  • Immunologic Memory
  • Immunotherapy*
  • Interleukin Receptor Common gamma Subunit / genetics
  • Interleukin Receptor Common gamma Subunit / immunology
  • Interleukin Receptor Common gamma Subunit / metabolism
  • Interleukin-15 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-2 / physiology*
  • Leukemia-Lymphoma, Adult T-Cell / genetics
  • Leukemia-Lymphoma, Adult T-Cell / immunology
  • Leukemia-Lymphoma, Adult T-Cell / therapy
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Regulatory / immunology
  • X-Linked Combined Immunodeficiency Diseases / genetics
  • X-Linked Combined Immunodeficiency Diseases / immunology
  • X-Linked Combined Immunodeficiency Diseases / therapy

Substances

  • Interleukin Receptor Common gamma Subunit
  • Interleukin-15
  • Interleukin-2
  • Receptors, Interleukin-2