The mechanism of splenic invariant NKT cell activation dictates localization in vivo.
The mechanism of splenic invariant NKT cell activation dictates localization in vivo.
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DOI：
10.4049/jimmunol.1300299
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发表时间：
2013-07-15
期刊：
影响因子：
--
通讯作者：
Leadbetter EA
中科院分区：
文献类型：
--
作者：
King IL;Amiel E;Tighe M;Mohrs K;Veerapen N;Besra G;Mohrs M;Leadbetter EA
不变自然杀伤T（iNKT）细胞是糖脂特异性先天淋巴细胞，在对各种感染和疾病的免疫反应中发挥着关键作用。iNKT细胞通过与负载脂质的抗原呈递细胞的同源相互作用、通过抗原非依赖性丝氨酸介导的信号传导途径或两者的组合被激活。虽然这些iNKT细胞活化模式中的每一种在指导体液和细胞介导的免疫应答中发挥重要作用，但这些相互作用的时空性质和活化的细胞要求在很大程度上是不确定的。结合新的原位共聚焦成像的α半乳糖神经酰胺负载的CD1d四聚体标记，以定位内源性iNKT细胞群体与细胞因子报告小鼠，我们揭示了早期小鼠脾脏iNKT细胞活化的编排在糖脂免疫和肺炎链球菌全身感染的不同设置。我们发现，iNKT细胞巩固在边缘区，并需要树突状细胞内衬脾边缘区激活同源糖脂管理后，在全身感染，但不以下外源性细胞因子管理。在进一步确定同源iNKT细胞与抗原呈递细胞相互作用的重要性的同时，我们还表明，非同源iNKT依赖性机制足以介导整个脾实质中的效应结果，如STAT信号传导和DC许可。总的来说，这些数据为iNKT细胞如何作为天然佐剂促进适应性免疫反应提供了新的见解，而不管它们的组织定位如何。
Invariant Natural Killer T (iNKT) cells are glycolipid-specific innate lymphocytes emerging as critical players in the immune response to diverse infections and disease. iNKT cells are activated either through cognate interactions with lipid-loaded antigen-presenting cells, by antigen-independent cytokine-mediated signaling pathways, or a combination of both. While each of these modes of iNKT cell activation play important roles in directing the humoral and cell-mediated immune response, the spatio-temporal nature of these interactions and the cellular requirements for activation are largely undefined. Combining novel in situ confocal imaging of αGalactosylceramide-loaded CD1d tetramer labeling to localize the endogenous iNKT cell population with cytokine reporter mice, we reveal the choreography of early murine splenic iNKT cell activation across diverse settings of glycolipid immunization and systemic infection with Streptococcus pneumoniae. We find that iNKT cells consolidate in the marginal zone and require dendritic cells lining the splenic marginal zone for activation following administration of cognate glycolipids and during systemic infection but not following exogenous cytokine administration. While further establishing the importance of cognate iNKT cell interactions with antigen-presenting cells, we also show that non-cognate iNKT-dependent mechanisms are sufficient to mediate effector outcomes such as STAT signaling and DC licensing throughout the entire splenic parenchyma. Collectively, these data provide new insight into how iNKT cells may serve as a natural adjuvant in facilitating adaptive immune responses irrespective of their tissue localization.
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影响因子：
3.7
作者：
Martens P;Worm SW;Lundgren B;Konradsen HB;Benfield T
通讯作者：
Benfield T
影响因子：
4.4
作者：
Farrand, Kathryn J.;Dickgreber, Nina;Hermans, Ian F.
通讯作者：
Hermans, Ian F.
DOI：
10.1073/pnas.0812247106
发表时间：
2009-02-03
影响因子：
11.1
作者：
Idoyaga, Juliana;Suda, Nao;Steinman, Ralph M.
通讯作者：
Steinman, Ralph M.
影响因子：
30.5
作者：
Lee, Woo-Yong;Moriarty, Tara J.;Kubes, Paul
通讯作者：
Kubes, Paul
未成熟的小鼠 NKT 细胞经历了发育程序化的先天性 IL-4 分泌阶段
影响因子：
5.5
作者：
Dickgreber, Nina;Farrand, Kathryn J.;Hermans, Ian F.
通讯作者：
Hermans, Ian F.