Centre National de la Recherche Scientifique/Université de Nice-Sophia Antipolis, Unité Mixte de Recherche 6097, Valbonne, France.
J Immunol. 2010 Aug 15;185(4):2174-81. doi: 10.4049/jimmunol.1001486. Epub 2010 Jul 12.
The ability of NK cells to rapidly produce IFN-gamma is an important innate mechanism of resistance to many pathogens including Leishmania major. Molecular and cellular components involved in NK cell activation in vivo are still poorly defined, although a central role for dendritic cells has been described. In this study, we demonstrate that Ag-specific CD4(+) T cells are required to initiate NK cell activation early on in draining lymph nodes of L. major-infected mice. We show that early IFN-gamma secretion by NK cells is controlled by IL-2 and IL-12 and is dependent on CD40/CD40L interaction. These findings suggest that newly primed Ag-specific CD4(+) T cells could directly activate NK cells through the secretion of IL-2 but also indirectly through the regulation of IL-12 secretion by dendritic cells. Our results reveal an unappreciated role for Ag-specific CD4(+) T cells in the initiation of NK cell activation in vivo upon L. major infection and demonstrate bidirectional regulations between innate and adaptive immunity.
NK 细胞能够快速产生 IFN-γ，这是抵抗包括利什曼原虫在内的许多病原体的重要先天机制。尽管树突状细胞（dendritic cells，DCs）起着核心作用，但体内 NK 细胞激活的分子和细胞成分仍未得到很好的定义。在这项研究中，我们证明了 Ag 特异性 CD4(+)T 细胞对于在利什曼原虫感染的小鼠引流淋巴结中早期启动 NK 细胞激活是必需的。我们表明，NK 细胞的早期 IFN-γ 分泌受 IL-2 和 IL-12 的控制，并且依赖于 CD40/CD40L 相互作用。这些发现表明，新激活的 Ag 特异性 CD4(+)T 细胞可以通过分泌 IL-2 直接激活 NK 细胞，也可以通过调节 DC 分泌 IL-12 间接激活 NK 细胞。我们的结果揭示了 Ag 特异性 CD4(+)T 细胞在利什曼原虫感染后体内 NK 细胞激活起始中的未被认识的作用，并证明了先天免疫和适应性免疫之间的双向调节。
