Macrophage- and Dendritic-Cell-Derived Interleukin-15 Receptor Alpha Supports Homeostasis of Distinct CD8+ T Cell Subsets
Macrophage- and Dendritic-Cell-Derived Interleukin-15 Receptor Alpha Supports Homeostasis of Distinct CD8+ T Cell Subsets
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DOI：
10.1016/j.immuni.2009.09.017
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发表时间：
2009-11-20
期刊：
影响因子：
32.4
通讯作者：
Ma, Averil
中科院分区：
文献类型：
--
作者：
Mortier, Erwan;Advincula, Rommel;Ma, Averil
白介素15受体α(IL-15Rα)是一种多向性表达的分子，其分子伴侣和转运蛋白可将IL-15传递给NK和T细胞。为了研究不同细胞呈递的IL-15Rα是否具有不同的生理功能，我们产生了四种不同细胞类型的缺失IL-15Rα的小鼠。我们发现，IL-15Rα在巨噬细胞上的表达，而不是树突状细胞(DC)上的表达，支持抗原特异性效应细胞CID T细胞向记忆细胞的早期转变。在记忆性CD8(+)T细胞分化后，DC上表达的IL-15Rα选择性地支持中央记忆性CD8(+)T细胞，而巨噬细胞上表达的IL-15Rα既支持中央记忆性CD8(+)T细胞，又支持效应记忆性CD8(+)T细胞。相比之下，巨噬细胞、树突状细胞或两者都缺乏IL-15Rα的小鼠，在NK细胞的动态平衡和激活方面表现出同等的缺陷。这些研究明确了巨噬细胞表达IL-15Rα的独特作用，并表明NK细胞依赖于不同的IL-15Rα依赖的IL-15信号，而不是记忆CD8(+)T细胞。此外，它们还展示了细胞因子信号的多样性、规范性和地理限制。
Interleukin-15 receptor alpha (IL-15R alpha) is a pleiotropically expressed molecule that chaperones and transpresents IL-15 to NK and T cells. To investigate whether IL-15R alpha presented by different cells perform distinct physiological functions, we have generated four lines of mice lacking IL-15R alpha in various cell types. We find that IL-15R alpha expression on macrophages but not dendritic cells (DCs) supports the early transition of antigen specific effector CID T cells to memory cells. After memory CD8(+) T cell differentiation, IL-15R alpha expression on DCs selectively supports central memory CD8(+) T cells, whereas IL-15R alpha expression on macrophages supports both central and effector memory CD8(+) T cells. By contrast, mice lacking IL-15R alpha on macrophages, DCs, or both, exhibit equivalent defects in NK cell homeostasis and activation. These studies define unique roles for macrophage expression of IL-15R alpha and show that NK cells rely upon distinct IL-15R alpha dependent IL-15 signals than memory CD8(+) T cells. Moreover, they demonstrate the diversity, specification, and geographic restriction of cytokine signals.