Propagation and control of T cell responses by heparan sulfate-bound IL-2

J Immunol. 2003 Jun 1;170(11):5470-4. doi: 10.4049/jimmunol.170.11.5470.

Abstract

IL-2, a cytokine produced by T cells, is a key regulator of immune responses and T cell homeostasis. Controlling the availability of IL-2 is consequently of significant import to the immune system. Like other cytokines, IL-2 is thought to function as a soluble agonist, transiently present when secreted in response to appropriate stimuli. In this study, we show that the most salient properties of IL-2, propagation and control of T cell responses, are mediated in vivo by bound and not free cytokine and specifically by heparan sulfate-bound IL-2. These findings necessitate a new look at how IL-2 regulates immune responses and support the notion that the microenvironment plays a determining role in modulating the character of immune responses.

Publication types

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

MeSH terms

  • Animals
  • Cell Division / genetics
  • Cell Division / immunology
  • Extracellular Matrix / immunology
  • Extracellular Matrix / metabolism
  • Heparan Sulfate Proteoglycans / metabolism
  • Heparan Sulfate Proteoglycans / physiology*
  • Homeostasis / genetics
  • Homeostasis / immunology
  • Interleukin-2 / deficiency
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukin-2 / physiology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Immunological
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Solubility
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Heparan Sulfate Proteoglycans
  • Interleukin-2