Nature immunology · 2026
Metabolic quiescence of naive-like memory T cells precedes and maintains antigen-specific T cell memory.
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Frischholz Sina, Schuster Ev-Marie, Grotz Myriam, Schülein Christine, Benz Julia, Kocher Katharina, Klotz Lucia, Varga Szilard, Hiltner Theresa, Alsalameh Rayya, Esse Jan, Träger Johannes, Held Jürgen, Graw Frederik, Pahle Jürgen, Spriewald Bernd, Gattinoni Luca, Buchholz Veit R, Drost Felix, Schubert Benjamin, Rothenfußer Simon, Busch Dirk H, Bogdan Christian, Schober Kilian
Аннотация
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.