Single-cell analysis by mass cytometry reveals metabolic states of early-activated CD8T cells during the primary immune response.

in Immunity by Lauren S Levine, Kamir J Hiam-Galvez, Diana M Marquez, Iliana Tenvooren, Matthew Z Madden, Diana C Contreras, Debolanle O Dahunsi, Jonathan M Irish, Olalekan O Oluwole, Jeffrey C Rathmell, Matthew H Spitzer

TLDR

  • This study investigates how T cells, which are part of our immune system, use energy to fight infections.
  • The study uses a special tool called mass cytometry to look at how T cells use energy at a very small level, called single-cell resolution.
  • The study found that early-activated T cells use a mix of energy sources, but most of them use a lot of energy from a process called glycolysis.
  • The study also found that this mix of energy sources changes over time, and that this change is important for T cells to fight infections effectively.

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 CD8T 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.

Overview

  • The study investigates the metabolic state of rare, early-activated T cells during an immune response.
  • The study uses mass cytometry to quantify metabolic regulators at single-cell resolution in parallel with cell signaling, proliferation, and effector function.
  • The study aims to understand how T cells arrive at their metabolic states during an immune response.

Comparative Analysis & Findings

  • The study reveals a distinct metabolic state in early-activated T cells characterized by maximal expression of glycolytic and oxidative metabolic proteins.
  • The cells in this transient state were most abundant 5 days post-infection before rapidly decreasing metabolic protein expression.
  • The study also observed similar findings in chimeric antigen receptor (CAR) T cells interrogated longitudinally in advanced lymphoma patients.

Implications and Future Directions

  • The study demonstrates the utility of single-cell metabolic analysis by mass cytometry to identify metabolic adaptations of immune cell populations in vivo.
  • The study provides a resource for investigations of metabolic regulation of immune responses across a variety of applications.
  • Future research directions could include investigating the role of metabolic regulation in immune cell function and identifying potential therapeutic targets for modulating immune cell metabolism.
Read Full Article