Yutaka Tagaya, Richard N. Bamford, IL-2 is primarily produced by activated T cells, Andrew P. DeFilippis, and Thomas A. Waldmann whereas there is no IL-15 mRNA demonstrable in normal Metabolism Branch, National Cancer Institute resting or activated T cells as assessed by Northern blot National Institutes of Health analysis. Nevertheless, there is widespread expression Bethesda, Maryland 20892 of IL-15 message, which appears most abundantly in placenta and skeletal muscle but also in kidney, lung, and heart as well as lipopolysaccharide (LPS)-activated Intercellular communications essential for regulatory monocytes (Grabsteinet al., 1994; Bamford etal., 1996). and effector actions involved in immune responses are The expression of the cytokine IL-2 is controlled preoften mediated by aseries of proteins termed cytokines. dominantly at the level of transcription and message Cytokines exhibit a high degree of redundancy and stabilization. In contrast, the synthesis and secretion of pleiotropy, controlling a wide range of functions in vari- IL-15 appears to be controlled at multiple levels (eg, ous cell types. The redundancy is explained in part by translation, and entry into secretory pathway) in addition the promiscuity of receptors; that is, by the sharing of to transcription (Bamford et al., 1996). An additional difcommonreceptorsubunitsamongmembersofthecyto- ference between IL-15 and IL-2 is that IL-15 uses a kine receptor family (Bazan, 1990; Sato and Miyajima, distinct receptor and signaling system in select cells. In 1994; Kishimoto et al., 1994). Each cytokine has its own particular, IL-15 stimulates the proliferation of mast cells private receptor but may also share a public receptor that do not respond to IL-2 (Tagaya et al., 1996). In with other cytokines. For example, receptors for in- such cells, IL-15 binding and signaling involves a novel terleukin-6 (IL-6), leukemia inhibitory factor, oncostatin receptor system that does not share any subunits with M, ciliary neurotropic factor, IL-11, and cardiotropin-1 the IL-2R system. Furthermore, this novel IL-15R system share a gp130 signaling unit, whereas IL-3, IL-5, and utilizes a signal transduction pathway distinct from the granulocyte/macrophage colony-stimulating factor uti- one used by the IL-2/IL-15R system in T cells. lize a common c receptor subunit (Sato and Miyajima 1994, Kishimoto et al. 1994). There is a similar sharing