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Propagation and Control of T Cell Responses by Heparan Sulfate-Bound IL-2¹

Lucile E. Wrenshall^2,*, Jeffrey L. Platt, Elliot T. Stevens^*, Thomas N. Wight and John D. Miller^*,

^* Division of Transplantation, Nebraska Medical Center, Omaha, NE 68198; Department of Immunology, Mayo Clinic, Rochester, MN 55905; and Division of Vascular Biology, Hope Heart Research Institute, Seattle, WA 98104

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.

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The JI 2003 170: 5343-5344. [Full Text]  

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