Tissue-Specific Distribution of iNKT Cells Impacts Their Cytokine Response.
Tissue-Specific Distribution of iNKT Cells Impacts Their Cytokine Response.
复制标题
DOI：
10.1016/j.immuni.2015.06.025
复制
发表时间：
2015-09-15
期刊：
影响因子：
32.4
通讯作者：
Hogquist KA
中科院分区：
文献类型：
--
作者：
Lee YJ;Wang H;Starrett GJ;Phuong V;Jameson SC;Hogquist KA
目前已鉴定出三种不变自然杀伤T细胞亚群，NKT1、NKT2和NKT17，它们在刺激时会产生不同的细胞因子，但对它们的定位知之甚少。在这里，我们定义了这些亚群的解剖定位和系统分布，并测量了它们的细胞因子产生。胸腺NKT2细胞在稳定状态下产生白介素4(IL-4)，位于髓质和条件髓质胸腺细胞中。NKT2细胞在BALB/c小鼠的肠系膜淋巴结(LN)中大量存在，并在调节其他淋巴细胞的T细胞区产生IL-4。静脉注射α-半乳糖神经酰胺可激活血管通路的NKT1细胞，但不能激活LN或胸腺NKT细胞，从而产生全身干扰素-γ和IL-4；口服α-半乳糖神经酰胺可激活肠系膜LN中的NKT2细胞，导致局部IL-4的释放。这些发现表明，iNKT细胞的定位控制着它们在稳态和激活时的细胞因子反应。
Three subsets of invariant natural killer T (iNKT) cells have been identified, NKT1, NKT2 and NKT17, which produce distinct cytokines when stimulated, but little is known about their localization. Here, we have defined the anatomic localization and systemic distribution of these subsets and measured their cytokine production. Thymic NKT2 cells that produced interleukin-4 (IL-4) at steady state were located in the medulla and conditioned medullary thymocytes. NKT2 cells were abundant in the mesenteric lymph node (LN) of BALB/c mice and produced IL-4 in the T cell zone that conditioned other lymphocytes. Intravenous injection of α-galactosylceramide activated NKT1 cells with vascular access, but not LN or thymic NKT cells, resulting in systemic interferon-γ and IL-4 production, while oral α-galactosylceramide activated NKT2 cells in the mesenteric LN, resulting in local IL-4 release. These finding indicate that the localization of iNKT cells governs their cytokine response both at steady state and upon activation.