Propagation and control of T cell responses by heparan sulfate-bound IL-2.
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.
Wrenshall
Lucile E
LE
Division of Transplantation, Nebraska Medical Center, Omaha, NE 68198-3285, USA. lwrenshall@surgery.unmc.edu
Platt
Jeffrey L
JL
Stevens
Elliot T
ET
Wight
Thomas N
TN
Miller
John D
JD
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D019812:Heparan Sulfate Proteoglycans; D007376:Interleukin-2