Frischholz et al. analyzed CD8+ T cells after yellow fever vaccination, and found that TEM and TCM phenotypes dominated the acute response at 14 days. However, a naive-like T memory population (TNM) comprised ~50% of the repertoire at 1 year, and remained for decades post-vaccination. At 14 days, TNM were characterized by quiescence, downregulated effector programs, low proliferation, and minimal apoptosis. This was in contrast to TCM, cycling, and effector-like populations, which contracted within 1-2 months. While all T cells primarily leveraged oxidative phosphorylation, TCM uniquely leveraged glycolysis, and TNM exclusively utilized OXPHOS.
Contributed by Morgan Janes
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.
Author Info: (1) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany
Author Info: (1) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (2) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (3) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (4) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (5) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (6) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (7) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (8) Department of Internal Medicine 5 - Hematology and Oncology, Friedrich-Alexander-Universitt Erlangen-Nrnberg (FAU) and Universittsklinikum Erlangen, Erlangen, Germany. Biological Information Processing Group, BioQuant, Heidelberg University, Heidelberg, Germany. (9) Institute for Medical Microbiology, Immunology, and Hygiene, School of Medicine and Health, Technical University of Munich, Munich, Germany. (10) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (11) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (12) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (13) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. (14) Department of Internal Medicine 5 - Hematology and Oncology, Friedrich-Alexander-Universitt Erlangen-Nrnberg (FAU) and Universittsklinikum Erlangen, Erlangen, Germany. Deutsches Zentrum Immuntherapie, FAU Erlangen-Nrnberg and Universittsklinikum Erlangen, Erlangen, Germany. (15) Biological Information Processing Group, BioQuant, Heidelberg University, Heidelberg, Germany. (16) Department of Internal Medicine 5 - Hematology and Oncology, Friedrich-Alexander-Universitt Erlangen-Nrnberg (FAU) and Universittsklinikum Erlangen, Erlangen, Germany. (17) Division of Functional Immune Cell Modulation, Leibniz Institute for Immunotherapy, Regensburg, Germany. University of Regensburg, Regensburg, Germany. Center for Immunomedicine in Transplantation and Oncology, University Hospital Regensburg, Regensburg, Germany. (18) Institute for Medical Microbiology, Immunology, and Hygiene, School of Medicine and Health, Technical University of Munich, Munich, Germany. Division of Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. (19) Institute of Computational Biology, Helmholtz Zentrum Mnchen - German Research Center for Environmental Health, Neuherberg, Germany. (20) Institute of Computational Biology, Helmholtz Zentrum Mnchen - German Research Center for Environmental Health, Neuherberg, Germany. (21) Institute of Clinical Pharmacology, LMU University Hospital, LMU Munich, Munich, Germany. Einheit fr Klinische Pharmakologie (EKLiP), Helmholtz Zentrum Mnchen German Research Center for Environmental Health (HMGU), Neuherberg, Germany. (22) Institute for Medical Microbiology, Immunology, and Hygiene, School of Medicine and Health, Technical University of Munich, Munich, Germany. German Center for Infection Research, Partner Site Munich, Munich, Germany. (23) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. FAU Profile Center Immunomedicine, FAU Erlangen-Nrnberg, Erlangen, Germany. (24) Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universittsklinikum Erlangen, Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, Germany. kilian.schober@uk-erlangen.de. FAU Profile Center Immunomedicine, FAU Erlangen-Nrnberg, Erlangen, Germany. kilian.schober@uk-erlangen.de.
