Levine LS, Hiam-Galvez KJ, Marquez DM, Tenvooren I, Madden MZ, Contreras DC, Dahunsi DO, Irish JM, Oluwole OO, Rathmell JC, Spitzer MH. Single-cell analysis by mass cytometry reveals metabolic states of early-activated CD8 T cells during the primary immune response. Immunity. 2021 Dec 13;54(54). 829-844.e5. PMID: 33705706 [PubMed] PMCID: PMC8046726 NIHMSID: NIHMS1678613.
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 5 days post-infection before rapidly decreasing metabolic protein expression. Analogous findings were observed in chimeric antigen receptor (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.