Single-cell analysis by mass cytometry reveals metabolic states of early-activated CD8(+) T cells during the primary immune response.
Single-cell analysis by mass cytometry reveals metabolic states of early-activated CD8(+) T cells during the primary immune response.
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DOI：
10.1016/j.immuni.2021.02.018
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发表时间：
2021-04-13
期刊：
影响因子：
32.4
通讯作者：
Spitzer MH
中科院分区：
文献类型：
--
作者：
Levine LS;Hiam-Galvez KJ;Marquez DM;Tenvooren I;Madden MZ;Contreras DC;Dahunsi DO;Irish JM;Oluwole OO;Rathmell JC;Spitzer MH
记忆T细胞被认为依赖于氧化磷酸化和糖酵解的短寿命效应T细胞。在这里，我们研究了T细胞如何在免疫应答过程中达到这些状态。为了了解罕见的早期活化T细胞的代谢状态，我们采用了质谱细胞术，以单细胞分辨率定量代谢调节因子，并与细胞信号传导、增殖和效应功能平行。我们在体外和体内对单核细胞增生李斯特菌感染的反应中询问了CD 8 + T细胞活化。这种方法揭示了一个独特的代谢状态，在早期活化的T细胞，其特征是糖酵解和氧化代谢蛋白的最大表达。这种瞬时状态的细胞在感染后5天最丰富，然后迅速降低代谢蛋白表达。在晚期淋巴瘤患者中纵向询问的CAR T细胞中观察到类似的发现。我们的研究证明了单细胞代谢分析的实用性，通过质谱细胞术来识别体内免疫细胞群的代谢适应，并为各种应用中免疫反应的代谢调节的研究提供了资源。Levine、Hiam-Galvez等人开发了一种基于质谱的方法来定量体内单细胞中的代谢蛋白表达，揭示了CD 8 + T细胞活化后早期的独特代谢状态，其特征在于糖酵解和氧化蛋白的同时表达。这种方法为各种应用中的代谢调节研究提供了资源。
Memory T cells are thought to rely on oxidative phosphorylation and short-lived effector T cells on glycolysis. Here, we investigated how T cells arrive at these states during an immune response. To understand the metabolic state of rare, early activated T cells, we adapted mass cytometry to quantify metabolic regulators at single-cell resolution in parallel with cell signaling, proliferation, and effector function. We interrogated CD8+ T cell activation in vitro and in response to Listeria monocytogenes infection in vivo. This approach revealed a distinct metabolic state in early activated T cells characterized by maximal expression of glycolytic and oxidative metabolic proteins. Cells in this transient state were most abundant five days post-infection before rapidly decreasing metabolic protein expression. Analogous findings were observed in CAR T cells interrogated longitudinally in advanced lymphoma patients. Our study demonstrates the utility of single-cell metabolic analysis by mass cytometry to identify metabolic adaptations of immune cell populations in vivo and provides a resource for investigations of metabolic regulation of immune responses across a variety of applications. Levine, Hiam-Galvez et al. develop a mass cytometry-based approach to quantify metabolic protein expression in single cells in vivo, revealing a distinct metabolic state early after CD8+ T cell activation characterized by simultaneous expression of glycolytic and oxidative proteins. This approach provides a resource for the study of metabolic regulation across a variety of applications.
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影响因子：
8.8
作者：
Chu T;Tyznik AJ;Roepke S;Berkley AM;Woodward-Davis A;Pattacini L;Bevan MJ;Zehn D;Prlic M
通讯作者：
Prlic M
DOI：
10.4049/jimmunol.1800705
发表时间：
2018-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cunningham CA;Hoppins S;Fink PJ
通讯作者：
Fink PJ
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
影响因子：
46.9
作者：
Good, Zinaida;Borges, Luciene;Bendall, Sean C.
通讯作者：
Bendall, Sean C.
DOI：
10.1016/0006-291x(92)90501-b
发表时间：
1992-03-16
影响因子：
3.1
作者：
CARPENTER, K;POLLITT, RJ;MIDDLETON, B
通讯作者：
MIDDLETON, B