摘要
IL-15 is critical for natural killer (NK)-cell development and function and for memory CD8(+) T-cell homeostasis. The IL-15 receptor consists of IL-15Ralpha, IL-2Rbeta, and the common cytokine receptor gamma chain (gamma(c)). IL-15Ralpha is known to "trans-present" IL-15 to an IL-2Rbeta/gamma(c) heterodimeric receptor on responding cells to initiate signaling. To investigate the importance of the IL-15Ralpha cytoplasmic domain, we generated a chimeric receptor consisting of the extracellular domain of IL-15Ralpha and intracellular domain of IL-2Ralpha (IL-15Ralpha(ext)/IL-2Ralpha(int)) and examined its function in 32D cells, in knock-in (KI) mice, and in adoptive-transfer experiments. The chimeric protein exhibited decreased cell-surface expression, and KI mice exhibited diminished NK, NKT, and CD8(+) T-cell development and defects in T-cell functional responses. However, 32D cells expressing the chimeric receptor had less IL-15-induced proliferation than wild-type (WT) transfectants with similar levels of IL-15Ralpha expression, indicating a signaling role for the IL-15Ralpha cytoplasmic domain beyond its effect on expression, and demonstrating that the IL-2Ralpha and IL-15Ralpha cytoplasmic domains are functionally distinct. Interestingly, adoptive-transfer experiments indicated that the chimeric IL-15Ralpha(ext)/IL-2Ralpha(int) receptor still supports trans-presentation. These experiments collectively indicate that IL-15Ralpha can act in cis in addition to acting in trans to present IL-15 to responding cells.
摘要译文
IL-15是用于自然杀伤（NK）β细胞的发育和功能以及用于记忆CD8（）的T细胞稳态的关键。所述IL-15受体包括IL-15Rα的IL-2Rbeta的，和普通的细胞因子受体γ链（γ-（c）项）。 IL-15Rα的是众所周知的“跨目前”IL-15到IL-2Rbeta /伽玛（三）在回答细胞启动信号异二聚体受体。调查的IL-15Rα胞胞质域的重要性，我们产生了嵌合受体选自由IL-15Rα的胞外结构域和IL-2Rα结合的胞内结构域的（IL-15Rα胞（分机）/ IL-2Rα结合（INT））和研究其功能在32D细胞，在敲入（KI）的小鼠，并在过继转移实验。表现出嵌合蛋白质减少细胞表面表达，和KI小鼠表现出减少的NK，NKT，和CD8（）的T细胞发育和缺陷在T细胞功能的应答。然而，32D细胞表达的嵌合受体有较少的IL-15诱导的增殖比野生型（WT）转染子与IL-15Rα的表达水平相似，指示用于超越其上表达的影响与IL-15Rα的胞质域的信令的作用，并表明与IL-2Rα结合和IL-15Rα的胞质域在功能上是不同的。有趣的是，过继转移实验表明，嵌合的IL-15Rα胞（分机）/ IL-2Rα结合（int）的受体仍支持反式介绍。这些实验集体表明，IL-15Rα的可顺除了采取行动，行动反式呈现IL-15响应细胞。
Wu Z; Xue HH; Bernard J; Zeng R; Issakov D; Bollenbacher-Reilley J; Belyakov IM; Oh S; Berzofsky JA; Leonard WJ. The IL-15 receptor {alpha} chain cytoplasmic domain is critical for normal IL-15Ralpha function but is not required for trans-presentation.[J]. Blood, 2008,112(12): 4411-4419