Mortier Erwan, Advincula Rommel, Kim Leesun, Chmura Stephen, Barrera Julio, Reizis Boris, Malynn Barbara A, Ma Averil
Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-0451, USA.
Immunity. 2009 Nov 20;31(5):811-22. doi: 10.1016/j.immuni.2009.09.017. Epub 2009 Nov 12.
Interleukin-15 receptor alpha (IL-15R alpha) is a pleiotropically expressed molecule that chaperones and trans-presents 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 CD8(+) 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.
白细胞介素-15受体α（IL-15Rα）是一种多效性表达的分子，它能陪伴并将IL-15呈递给自然杀伤细胞（NK细胞）和T细胞。为了研究不同细胞所呈递的IL-15Rα是否具有不同的生理功能，我们构建了四组在不同细胞类型中缺乏IL-15Rα的小鼠品系。我们发现，巨噬细胞而非树突状细胞（DC）上的IL-15Rα表达支持抗原特异性效应CD8⁺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上的IL-15Rα表达选择性地支持中枢记忆性CD8⁺T细胞，而巨噬细胞上的IL-15Rα表达则支持中枢记忆性和效应性记忆CD8⁺T细胞。相比之下，巨噬细胞、DC或两者均缺乏IL-15Rα的小鼠在NK细胞稳态和激活方面表现出同等缺陷。这些研究明确了巨噬细胞表达IL-15Rα的独特作用，并表明NK细胞依赖于与记忆性CD8⁺T细胞不同的IL-15Rα依赖性IL-15信号。此外，它们还证明了细胞因子信号的多样性、特异性和空间限制。
