Interleukin 15 (IL-15) is a 14 kDa cytokine that is structurally and functionally related to IL- 2(1-3). Mature human IL-15 shares 70% amino acid sequence identity with mouse and rat IL-15. Alternate splicing generates isoforms of IL-15 with either a long or short signal peptide (LSP or SSP), and the SSP isoform is retained intracellularly (4). IL-15 associates with IL-15 Rα in the endoplasmic reticulum, and this complex is expressed on the cell surface (5, 6). The dominant mechanism of IL-15 action is known as transpresentation in which IL-15 and IL-15 Rα are coordinately expressed on the surface of one cell and interact with complexes of IL-2 Rβ/γc on adjacent cells (7). This enables cells to respond to IL-15 even if they do not express IL-15 Rα (6, 8). Consistent with its shared use of IL-2 receptor subunits, IL-15 induces IL-2-like effects in lymphocyte development and homeostasis (3). It is particularly important for the maintenance and activation of NK cells and CD8+ memory T cells (3). IL-15 also exerts pleiotropic effects on other hematopoietic cells and nonimmune cells (2). Ligation of membraneassociated IL-15/IL-15Rα complexes induces reverse signaling that promotes cellular adhesion, tyrosine phosphorylation of intracellular proteins, and cytokine secretion by the IL-15/IL-15Rα expressing cells (9, 10).