Regulation of T cell homeostasis by heparan sulfate-bound IL-2.
Although IL-2 is commonly thought to promote proliferation of T lymphocytes, mice deficient in IL-2 exhibit splenomegaly, lymphocytosis, and autoimmunity, suggesting this cytokine may have a prominent role in T cell homeostasis. Since the number of T cells in the bloodstream and lymphoid organs is tightly controlled, it is likely that the availability of IL-2 must also be closely regulated. One mechanism altering the local availability of cytokines is association with heparan sulfate, a glycosaminoglycan found on cell surfaces and within extracellular matrices. Here we show that an association between IL-2 and heparan sulfate localizes IL-2 to lymphoid organs such as the spleen. We also show that IL-2, sequestered in this way, contributes to the activation of T lymphocytes and primes T lymphocytes for activation-induced cell death.
Wrenshall
L E
LE
Department of Surgery, University of Washington, Seattle 98195, USA. lew@u.washington.edu
Platt
J L
JL
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D006025:Glycosaminoglycans / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009928:Organ Specificity / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*
D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007376:Interleukin-2