The Pleiotropic Functions of Interleukin 15: Not so Interleukin 2–Like after All

Since its discovery in 1994, IL-15 has been studied in the context of its structural cousin, IL-2 1. Early biochemical and in vitro lymphocyte studies revealed many similarities between IL-15 and IL-2: (a) IL-2 and IL-15 constitute the only two members of a family of cytokines containing a four α helix bundle; (b) the heterotrimeric receptors for IL-2 and IL-15 share both the IL-2/15Rβ and IL-2R common γ (IL-2Rγ or γc) chains; (c) the shared IL-2/15Rβ and γc chains are responsible for downstream cytoplasmic signals; and (d) the IL-2Rα and IL-15Rα chains, which confer specificity to IL-2R and IL-15R for their respective ligands, are closely related proteins 2. However, the highly restricted expression of IL-2 and IL-2Rα to activated T cells suggests that IL-2R signals perform unique functions in adaptive T cells, whereas the pleiotropic expression of...