Chu et al. demonstrated that a diverse set of precursor T cells were formed in the early phase of an acute infection, including cells with transcriptomic and epigenetic profiles resembling exhausted T cells from chronic infections. The precursors of exhausted T cells (Tpex) occurred early (day 4.5) and independently of the outcome of the infection. Strong TCR signaling was required for the formation of a long-lived Tpex population, while PD-1 signaling restricted the generation of Tpex in acute infection. Tpex appeared in similar numbers to memory precursor T cells, but declined substantially as infections resolved.
Contributed by Shishir Pant
ABSTRACT: T cell exhaustion limits effector T cell function in chronic infection and tumors(1,2). The development of these hypofunctional T cells and of their precursors was considered to require stimulatory conditions met only upon persisting exposure to antigen and inflammation. In sharp contrast, we found similar T cell populations in the early phase of acute infections(1,2). At that stage early developing TCF1(+) precursor population shows an unexpected diversity, which includes precursors of normal memory T cells but also cells with a phenotype, gene-expression, and epigenetic profile that resembles precursors of exhausted T cells found in chronic infections. We demonstrate that high ligand affinity promotes, and PD-1 signaling restricts the development of these precursors. While these exhausted precursors are initially frequently found, they decline without being completely lost in infections the immune system resolves. We therefore concluded that precursor T cells with at least two distinct phenotypes are preemptively generated irrespectively of the outcome of the infection.
Author Info: (1) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Cancer Immunology, Department of Biomedi
Author Info: (1) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Cancer Immunology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland. (2) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. ming.wu@tum.de. (3) Institute of Computational Biology, Helmholtz Zentrum Mnchen Deutsches Forschungszentrum fr Gesundheit und Umwelt (GmbH), Neuherberg, Germany. Department of Informatics, Technical University of Munich (TUM), Garching, Germany. (4) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (5) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (6) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (7) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (8) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (9) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (10) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (11) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Institute of Molecular Immunology, School of Medicine and Health, Technical University of Munich, Freising, Germany. (12) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (13) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (14) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (15) Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA. (16) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. (17) Cancer Immunology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland. (18) Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. Institute of Molecular Immunology, School of Medicine and Health, Technical University of Munich, Freising, Germany. (19) Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. matthias.heinig@helmholtz-muenchen.de. Institute of Computational Biology, Helmholtz Zentrum Mnchen Deutsches Forschungszentrum fr Gesundheit und Umwelt (GmbH), Neuherberg, Germany. matthias.heinig@helmholtz-muenchen.de. (20) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. carl-philipp.hackstein@tum.de. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. carl-philipp.hackstein@tum.de. Institute of Molecular Immunology, School of Medicine and Health, Technical University of Munich, Freising, Germany. carl-philipp.hackstein@tum.de. (21) Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. dietmar.zehn@tum.de. Center for Infection Prevention (ZIP), School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. dietmar.zehn@tum.de.
