CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell-like Populations and Diverse Mononuclear Phagocytes.
CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell-like Populations and Diverse Mononuclear Phagocytes.
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DOI：
10.4049/jimmunol.1600959
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Hurlstone AF
中科院分区：
文献类型：
--
作者：
Dee CT;Nagaraju RT;Athanasiadis EI;Gray C;Fernandez Del Ama L;Johnston SA;Secombes CJ;Cvejic A;Hurlstone AF
CD4+ T 细胞是免疫系统先天性和适应性臂的纽带。然而，人们对 CD4+ T 细胞的进化史知之甚少，也不清楚它们分化为特殊亚群的能力在早期脊椎动物中是否保守。在这项研究中，我们创造了带有鲜艳标记的 CD4+ 细胞的转基因斑马鱼，使我们能够在体内仔细观察硬骨鱼 CD4+ 白细胞的发育和特化。我们提供了进一步的证据，表明 CD4+ 巨噬细胞具有古老的起源，并且已经在硬骨鱼中出现。我们通过对硬骨鱼 CD4+ T 细胞和单核吞噬细胞之间的密切接触进行成像，证明了这种斑马鱼资源在细胞分辨率下探究免疫细胞复杂行为的实用性。最重要的是，我们揭示了体内硬骨鱼 CD4+ T 细胞的保守亚特化。我们证明，古老且特殊的鳃组织含有表达 il-4/13b 的 Th2 样细胞，但它们不共表达 il-4/13a。此外，我们还发现了斑马鱼肠道粘膜中存在的调节性 T 细胞样细胞群，与哺乳动物肠道中发现的细胞明显相似。最后，我们证明，与哺乳动物一样，斑马鱼 CD4+ T 细胞将浸润黑色素瘤肿瘤并获得与 2 型免疫微环境一致的表型。我们预计这一独特的资源对于未来生物医学研究中 T 细胞功能的研究、水产养殖中疫苗接种和健康管理的发展以及适应性免疫进化的进一步研究将具有无价的价值。
CD4+ T cells are at the nexus of the innate and adaptive arms of the immune system. However, little is known about the evolutionary history of CD4+ T cells, and it is unclear whether their differentiation into specialized subsets is conserved in early vertebrates. In this study, we have created transgenic zebrafish with vibrantly labeled CD4+ cells allowing us to scrutinize the development and specialization of teleost CD4+ leukocytes in vivo. We provide further evidence that CD4+ macrophages have an ancient origin and had already emerged in bony fish. We demonstrate the utility of this zebrafish resource for interrogating the complex behavior of immune cells at cellular resolution by the imaging of intimate contacts between teleost CD4+ T cells and mononuclear phagocytes. Most importantly, we reveal the conserved subspecialization of teleost CD4+ T cells in vivo. We demonstrate that the ancient and specialized tissues of the gills contain a resident population of il-4/13b–expressing Th2-like cells, which do not coexpress il-4/13a. Additionally, we identify a contrasting population of regulatory T cell–like cells resident in the zebrafish gut mucosa, in marked similarity to that found in the intestine of mammals. Finally, we show that, as in mammals, zebrafish CD4+ T cells will infiltrate melanoma tumors and obtain a phenotype consistent with a type 2 immune microenvironment. We anticipate that this unique resource will prove invaluable for future investigation of T cell function in biomedical research, the development of vaccination and health management in aquaculture, and for further research into the evolution of adaptive immunity.
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影响因子：
6.7
作者：
Kara EE;Comerford I;Fenix KA;Bastow CR;Gregor CE;McKenzie DR;McColl SR
通讯作者：
McColl SR
影响因子：
12.3
作者：
Lun AT;Bach K;Marioni JC
通讯作者：
Marioni JC
影响因子：
3.7
作者：
Kono T;Korenaga H
通讯作者：
Korenaga H
影响因子：
6.7
作者：
Hammarén MM;Oksanen KE;Nisula HM;Luukinen BV;Pesu M;Rämet M;Parikka M
通讯作者：
Parikka M
影响因子：
20.3
作者：
Balla, Keir M.;Lugo-Villarino, Geanncarlo;Traver, David
通讯作者：
Traver, David