# Metabolic quiescence of naive-like memory T cells precedes and maintains antigen-specific T cell memory

## TL;DR

This study shows that certain T cells become metabolically inactive after vaccination, which helps them survive long-term in the body.

## Contribution

The study reveals that naive-like memory T cells are metabolically quiescent and are preferentially maintained for long-term immunity.

## Key findings

- CD8+ central memory T cells are the most metabolically active during the acute phase after vaccination.
- Naive-like memory T cells are metabolically quiescent and are maintained 26 years postvaccination.
- Metabolic shutdown occurs in effector T cells during the acute immune response.

## Abstract

Metabolic activity shapes cell fate but remains challenging to capture in vivo with high resolution. Here we performed longitudinal metabolic and phenotypic profiling of human antigen-specific CD8+ T cells after yellow fever vaccination using flow cytometry and single-cell RNA sequencing. As assessed by protein translation rates, CD8+ T cells upregulated glycolysis to fuel anabolic needs for proliferation but predominantly used oxidative phosphorylation for energy production during the acute phase (days 7–28) after vaccination. Simultaneously, CD8+CD62L+CD45RA− central memory T cells were the most metabolically active subset, whereas CD8+CD62L−CD45RA+ effector T cells underwent metabolic shutdown. Weakly differentiated CD8+CD62L+CD45RA+CD95− naive-like memory T cells showed minimal activity, relied solely on oxidative phosphorylation and were preferentially maintained 26 years postvaccination, reinforcing the link between cellular quiescence and longevity. Our study highlights quiescence as a key feature for long-term immunological memory formation in humans.

Schober and colleagues show that effector CD8+ T cells undergo metabolic shutdown, CD8+ central memory T cells are the most metabolically active, and naive-like memory T cells are quiescent during the acute phase of the immune response and represent the dominant population of memory CD8+ T cells after yellow fever vaccination in humans.