Chae D W, Nosaka Y, Strom T B, Maslinski W
Harvard Medical School, Department of Medicine, Beth Israel Hospital, Boston, MA 02215, USA.
J Immunol. 1996 Oct 1;157(7):2813-9.
IL-15, a newly described cytokine exerting IL-2-like in vitro activities, binds to and induces proliferation of cells co-expressing IL-15R alpha, IL-2R beta, and IL-2R gamma chains. To study the expression of human IL-15R alpha chains, we have utilized tagged human IL-15 protein and FACS analysis. In contrast to resting cells, mitogen-activated macrophages, NK cells, and CD4+ and CD8+ T cells express IL-15R alpha chains. Neither IL-2R alpha nor IL-2R beta chains are required for IL-15 binding. Dexamethasone, but not cyclosporine or rapamycin, blocks mitogen-induced IL-15R alpha expression. Dexamethasone-pretreated cells respond to IL-15 poorly, while the response to IL-2 is not affected. Thus, despite structural and functional similarities between IL-2R alpha and IL-15R alpha chains, the activation-triggered mechanisms of induction are different. Since IL-15R alpha chain is necessary and sufficient for IL-15 binding, regulation of IL-15R alpha expression may represent a new target for T cell-directed pharmacologic intervention.
白细胞介素-15(IL-15)是一种新描述的细胞因子,在体外具有类似白细胞介素-2(IL-2)的活性,它能与共表达IL-15Rα、IL-2Rβ和IL-2Rγ链的细胞结合并诱导其增殖。为了研究人IL-15Rα链的表达,我们利用了带有标签的人IL-15蛋白和荧光激活细胞分选(FACS)分析。与静息细胞不同,有丝分裂原激活的巨噬细胞、自然杀伤(NK)细胞以及CD4⁺和CD8⁺T细胞表达IL-15Rα链。IL-15结合不需要IL-2Rα链和IL-2Rβ链。地塞米松可阻断有丝分裂原诱导的IL-15Rα表达,而环孢素或雷帕霉素则不能。经地塞米松预处理的细胞对IL-15反应较差,而对IL-2的反应不受影响。因此,尽管IL-2Rα链和IL-15Rα链在结构和功能上有相似之处,但激活触发的诱导机制是不同的。由于IL-15Rα链对于IL-15结合是必需且充分的,IL-15Rα表达的调节可能代表了针对T细胞的药物干预的新靶点。