TY - JOUR T1 - Single-cell metabolic dynamics of early activated CD8 T cells during the primary immune response to infection JF - bioRxiv DO - 10.1101/2020.01.21.911545 SP - 2020.01.21.911545 AU - Lauren S. Levine AU - Kamir J. Hiam AU - Diana M. Marquez AU - Iliana Tenvooren AU - Diana C. Contreras AU - Jeffrey C. Rathmell AU - Matthew H. Spitzer Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/10/2020.01.21.911545.abstract N2 - Memory T cells conventionally rely on oxidative phosphorylation and short-lived effector T cells on glycolysis. Here, we investigate how T cells arrive at these states during an immune response. In order 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 as well as the trajectory of CD8 T cells responding to Listeria monocytogenes infection, a well-characterized in vivo model for studies of T cell differentiation. This approach revealed a unique metabolic state in early activated T cells characterized by maximal expression of glycolytic and oxidative metabolic proteins. Peak utilization of both pathways was confirmed by extracellular flux analysis. Cells in this transient state were most abundant five days post-infection before rapidly downregulating metabolic protein expression. This approach should be useful for mechanistic investigations of metabolic regulation of immune responses.Competing Interest StatementM.H.S. has been a paid consultant for Five Prime Therapeutics, Ono Pharmaceutical and January, Inc. and has received funding support from Roche/Genentech, Pfizer, Valitor Inc., and Bristol-Myers Squibb. J.C.R. is a founder and member of the scientific advisory board of Sitryx Therapeutics, and member of the scientific advisory boards of Caribou Biosciences, Istesso Ltd, has received research funding from Kadmon, Incyte, Tempest, and Calithera, and received honorarium from Merck and Pfizer. ER -