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

Immunity. 2021 Apr 13;54(4):829-844.e5. doi: 10.1016/j.immuni.2021.02.018. Epub 2021 Mar 10.

Abstract

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.

Keywords: CD8 T cell; T cell activation; immunometabolism; mass cytometry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation / physiology
  • Female
  • Glycolysis / immunology
  • Immunologic Memory / immunology
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology
  • Listeriosis / microbiology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oxidative Phosphorylation
  • Receptors, Chimeric Antigen / immunology
  • Signal Transduction / immunology*
  • Single-Cell Analysis / methods

Substances

  • Receptors, Chimeric Antigen