Despite the expression of IL-15 mRNA in many cell types, the secreted protein is rarely detectable in biological samples. Recent research suggests that IL-15 is retained inside the cell and is only secreted in complex with its unique receptor, IL-15Rα. This chaperoning is required from the ER to Golgi through to secretion. The cytokine/receptor complex may stay bound to the cell surface, where it can be transpresented to cells expressing the βγ subunits of the receptor, or may be secreted in a soluble form that lacks the transmembrane domain of the receptor. The soluble IL-15/IL-15R complex is produced by mouse dendritic cells, fibroblasts, and macrophages, and demonstrates a 10- 100-fold increase in agonistic activity over IL-15 alone.