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
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Division / genetics
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Cell Division / immunology
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Extracellular Matrix / immunology
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Extracellular Matrix / metabolism
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Heparan Sulfate Proteoglycans / metabolism
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Heparan Sulfate Proteoglycans / physiology*
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Homeostasis / genetics
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Homeostasis / immunology
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Interleukin-2 / deficiency
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Interleukin-2 / physiology*
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Transgenic
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Models, Immunological
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Protein Binding / genetics
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Protein Binding / immunology
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Solubility
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
Substances
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Heparan Sulfate Proteoglycans
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Interleukin-2