Morvan Maelig G, Champsaur Marine, Reizis Boris, Lanier Lewis L
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.
Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94143.
Immunohorizons. 2017 May 1;1(3):10-19. doi: 10.4049/immunohorizons.1700004.
To investigate how dendritic cells (DCs) interact with NK cells in vivo, we developed a novel mouse model in which Rae-1ε, a ligand of the NKG2D receptor, is expressed in cells with high levels of CD11c. In these CD11c-Rae1 mice, expression of Rae-1 was confirmed on all subsets of DCs and a small subset of B and T cells, but not on NK cells. DC numbers and activation status were unchanged, and NK cells in these CD11c-Rae1 mice presented the same Ly49 repertoire and maturation levels as their littermate wildtype controls. Early NK cell activation after mouse CMV infection was slightly lower than in wildtype mice, but NK cell expansion and viral control were comparable. Notably, we demonstrate that chronic interaction of NK cells with NKG2D ligand-expressing DCs leads to a reversible NKG2D down-modulation, as well as impaired NKG2D-dependent NK cell functions, including tumor rejection. In addition to generating a useful mouse model, our studies reveal in vivo the functional importance of the NK cell and DC cross-talk.
为了研究树突状细胞（DCs）在体内如何与自然杀伤细胞（NK细胞）相互作用，我们构建了一种新型小鼠模型，其中NKG2D受体的配体Rae-1ε在高表达CD11c的细胞中表达。在这些CD11c-Rae1小鼠中，Rae-1在所有DC亚群以及一小部分B细胞和T细胞上的表达得到证实，但在NK细胞上未检测到。DC的数量和激活状态未发生变化，这些CD11c-Rae1小鼠中的NK细胞与同窝野生型对照相比，具有相同的Ly49谱系和成熟水平。小鼠巨细胞病毒感染后早期NK细胞的激活略低于野生型小鼠，但NK细胞的扩增和病毒控制情况相当。值得注意的是，我们证明NK细胞与表达NKG2D配体的DCs的长期相互作用会导致NKG2D的可逆性下调，以及NKG2D依赖性NK细胞功能受损，包括肿瘤排斥反应。除了构建一个有用的小鼠模型外，我们的研究还在体内揭示了NK细胞与DC相互作用的功能重要性。
