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<p>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<sup>+</sup> T cells after yellow fever vaccination using flow cytometry and single-cell RNA sequencing. As assessed by protein translation rates, CD8<sup>+</sup> 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<sup>+</sup>CD62L<sup>+</sup>CD45RA<sup>−</sup> central memory T cells were the most metabolically active subset, whereas CD8<sup>+</sup>CD62L<sup>−</sup>CD45RA<sup>+</sup> effector T cells underwent metabolic shutdown. Weakly differentiated CD8<sup>+</sup>CD62L<sup>+</sup>CD45RA<sup>+</sup>CD95<sup>−</sup> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月24日

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  • Sina Frischholz,
  • Ev-Marie Schuster,
  • Myriam Grotz,
  • Christine Schülein,
  • Julia Benz,
  • Katharina Kocher,
  • Lucia Klotz,
  • Szilard Varga,
  • Theresa Hiltner,
  • Rayya Alsalameh,
  • Jan Esse,
  • Johannes Träger,
  • Jürgen Held,
  • Frederik Graw,
  • Jürgen Pahle,
  • Bernd Spriewald,
  • Luca Gattinoni,
  • Veit R. Buchholz,
  • Felix Drost,
  • Benjamin Schubert,
  • Simon Rothenfußer,
  • Dirk H. Busch,
  • Christian Bogdan,
  • Kilian Schober

摘要

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.