Single-cell analysis by mass cytometry reveals metabolic states of early-activated CD8+ T cells during the primary immune response.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Levine, LS; Hiam-Galvez, KJ; Marquez, DM; Tenvooren, I; Madden, MZ; Contreras, DC; Dahunsi, DO; Irish, JM; Oluwole, OO; Rathmell, JC; Spitzer, MH

Published Date

  • April 13, 2021

Published In

Volume / Issue

  • 54 / 4

Start / End Page

  • 829 - 844.e5

PubMed ID

  • 33705706

Pubmed Central ID

  • PMC8046726

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2021.02.018

Language

  • eng

Conference Location

  • United States