Multieffector-functional immune responses of HMBPP-specific Vγ2Vδ2 T cells in nonhuman primates inoculated with Listeria monocytogenes ΔactA prfA*.
Multieffector-functional immune responses of HMBPP-specific Vγ2Vδ2 T cells in nonhuman primates inoculated with Listeria monocytogenes ΔactA prfA*.
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非人类灵长类动物中HMBPP特异性Vγ2Vδ2T细胞的多功能功能免疫反应接种了单核细胞增生李斯特菌ΔActaprfa*。
DOI：
10.4049/jimmunol.1200641
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发表时间：
2012-08-01
期刊：
影响因子：
--
通讯作者：
Chen ZW
中科院分区：
文献类型：
--
作者：
Ryan-Payseur B;Frencher J;Shen L;Chen CY;Huang D;Chen ZW
虽然单核细胞增多性李斯特氏菌可引起全身感染，导致自然流产、败血症和脑膜炎，但尚未有研究对人类抗L。单核细胞增多性免疫反应，包括抗原特异性Vγ2Vδ2T细胞的免疫反应，这是人类γδT细胞的一个主要亚群。单核细胞增多性李斯特菌是目前已知的唯一同时具有甲氧丙戊酸和非甲戊二酸异戊二烯生物合成途径的病原体，该途径可产生代谢磷酸盐或磷抗原激活人V-γ-2V-δ-2T细胞，因此在体内探索抗-L。V-γ-2V-δ-2T细胞的单核细胞增殖免疫反应在这项研究中，我们证明了恒河猴的亚临床系统性单核细胞增多性李斯特氏菌感染，通过肠外接种或接种减毒李斯特菌株，诱导了磷抗原特异性Vγ2Vδ2T细胞的多效应功能免疫反应。亚临床全身性感染和再感染减毒单核细胞增多性李斯特菌后，Vγ2Vδ2T细胞具有贴壁扩增和适应性或回忆性扩增的能力。扩增的V-γ-2V-δ-2T细胞可在肺间室和肠粘膜内运输和积聚。扩增的Vγ2Vδ2T细胞在感染L.单核细胞后可分化为产生干扰素γ、肿瘤坏死因子α、IL 4、IL 17或穿孔素的效应细胞，部分Vγ2Vδ2T细胞可同时产生IL 17和干扰素γ、IL 4和干扰素γ或α和穿孔素。令人惊讶的是，在体内扩增的Vγ2Vδ2T效应细胞在亚临床单核细胞增多性李斯特菌感染中可以直接溶解感染单核细胞增多性乳杆菌的靶细胞，并抑制细胞内的单核细胞增多性李斯特菌。因此，据我们所知，我们首次展示了多效应功能的Vγ2Vδ2T细胞对单核细胞增多性李斯特菌的反应。
Although Listeria monocytogenes can induce systemic infection causing spontaneous abortion, septicemia, and meningitis, studies have not been performed to investigate human anti-L. monocytogenes immune responses, including those of Ag-specific Vγ2Vδ2 T cells, a dominant human γδ T cell subset. L. monocytogenes is the only pathogen known to possess both the mevalonate and non-mevalonate isoprenoid biosynthesis pathways that produce metabolic phosphates or phosphoantigens activating human Vγ2Vδ2 T cells, making it interesting to explore in vivo anti-L. monocytogenes immune responses of Vγ2Vδ2 T cells. In this study, we demonstrated that subclinical systemic L. monocytogenes infection of rhesus macaques via parenteral inoculation or vaccination with an attenuated Listeria strain induced multieffector-functional immune responses of phosphoantigen-specific Vγ2Vδ2 T cells. Subclinical systemic infection and reinfection with attenuated L. monocytogenes uncovered the ability of Vγ2Vδ2 T cells to mount expansion and adaptive or recall-like expansion. Expanded Vγ2Vδ2 T cells could traffic to and accumulate in the pulmonary compartment and intestinal mucosa. Expanded Vγ2Vδ2 T cells could evolve into effector cells producing IFN-γ, TNF-α, IL-4, IL-17, or perforin after L. monocytogenes infection, and some effector Vγ2Vδ2 T cells could coproduce IL-17 and IFN-γ, IL-4 and IFN-γ, or TNF-α and perforin. Surprisingly, in vivo-expanded Vγ2Vδ2 T effector cells in subclinical L. monocytogenes infection could directly lyse L. monocytogenes-infected target cells and inhibit intracellular L. monocytogenes bacteria. Thus, we present the first demonstration, to our knowledge, of multieffector-functional Vγ2Vδ2 T cell responses against L. monocytogenes.
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DOI：
10.1073/pnas.0811250106
发表时间：
2009-05-05
影响因子：
11.1
作者：
Huang, Dan;Chen, Crystal Y.;Chen, Zheng W.
通讯作者：
Chen, Zheng W.
影响因子：
32.4
作者：
Hegazy, Ahmed N.;Peine, Michael;Loehning, Max
通讯作者：
Loehning, Max
影响因子：
4.4
作者：
Ali, Zahida;Shao, Lingyan;Chen, Zheng W.
通讯作者：
Chen, Zheng W.
影响因子：
3.1
作者：
Huang, Dan;Shen, Yun;Chen, Zheng W.
通讯作者：
Chen, Zheng W.
影响因子：
32.4
作者：
HARTY, JT;BEVAN, MJ
通讯作者：
BEVAN, MJ