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Frischholz, S.* ; Schuster, E.M.* ; Grotz, M.* ; Schülein, C.* ; Benz, J.* ; Kocher, K.* ; Klotz, L.* ; Varga, S.* ; Hiltner, T.* ; Alsalameh, R.* ; Esse, J.* ; Träger, J.* ; Held, J.* ; Graw, F.* ; Pahle, J.* ; Spriewald, B.* ; Gattinoni, L.* ; Buchholz, V.R.* ; Drost, F. ; Schubert, B. ; Rothenfußer, S. ; Busch, D.H.* ; Bogdan, C.* ; Schober, K.*

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

Nat. Immunol. 27, 452-462 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cytotoxic T Cell ; Cd8 ; Oxidative Phosphorylation ; Flow Cytometry ; Downregulation And Upregulation ; Glycolysis ; T Cell ; Cd28 ; Effector; Effector Function; Differentiation; Immunometabolism
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Journal Nature Immunology
Quellenangaben Volume: 27, Issue: 3, Pages: 452-462 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Unit for Clinical Pharmacology (KKG-EKLiP)
Grants Further funding came from the Hightech Agenda Bavaria to F.G.
This work was mainly supported by the BMFTR (Bundesministerium fr Forschung, Technologie und Raumfahrt
engl. Federal Ministry of Research, Technology and Space, projects 01KI2013 and 031L0290B to KS). Note: The BMFTR was formerly known as the BMBF (
Else Krner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation)
Further funding by grants of the iMed consortium of the German Helmholtz Societies to S.R.
Deutsche Forschungsgemeinschaft (German Research Foundation)
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
This work was supported by the BMFTR (Bundesministerium fr Forschung, Technologie und Raumfahrt
engl. Federal Ministry of Research, Technology and Space, project 031L0290A to B.Sc.). Note: The BMFTR was formerly known as the BMBF (engl. Federal Mini
Agence Nationale de la Recherche (French National Research Agency))
Boehringer Ingelheim Stiftung (Boehringer Ingelheim Foundation)
Klaus Tschira Stiftung (Klaus Tschira Foundation)