Regulation of T cell homeostasis by heparan sulfate-bound IL-21

Although IL-2 is commonly thought to promote proliferation of T lymphocytes , mice deficient in IL-2 exhibit splenomegaly, lymphocytosis, and autoimmun ity, suggesting this cytokine may have a prominent role in T cell homeostas is, Since the number of T cells in the bloodstream and lymphoid organs is t ightly controlled, it is likely that the availability of IL-2 must also be closely regulated. One mechanism altering the local availability of cytokin es is association with heparan sulfate, a glycosaminoglycan found on cell s urfaces 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 t o the activation of T lymphocytes and primes T lymphocytes for activation-i nduced cell death.