Interleukin‐15 up‐regulates interleukin‐2 receptor α chain but down‐regulates its own high‐affinity binding sites on human T and B cells

Abstract

The cytokines interleukin (IL)‐2 and IL‐15 share many biological activities as a consequence of their utilization of the β and γ chains of the IL‐2 receptor. However, each cytokine binds to a specific receptor α chain; IL‐2 with low affinity and IL‐15 with high affinity. Here, we demonstrate that IL‐15, like IL‐2, up‐regulates expression of IL‐2Rα on human T and B cells, but rapidly down‐regulates IL‐15 high‐affinity binding sites, which represent IL‐15Rα. This leads to a decreased responsiveness to IL‐15 as measured by induction of Jak3 tyrosine phosphorylation. These results suggest a mechanism by which IL‐15, a product of activated macrophages, may cooperate with IL‐2 at the initiation of an immune response and enhance subsequent IL‐2 responsiveness during T cell expansion.