@article{d295532296734b54b34c7f8aba06fb90,
title = "Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells",
abstract = " Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10–20% of all peripheral CD8 + T cells in mice. Their origin, biological roles, and relationship to na{\"i}ve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells. First, virtual memory T cells originate exclusively from strongly self-reactive T cells. Second, the stoichiometry of the CD8 interaction with Lck regulates the size of the virtual memory T-cell compartment via modulating the self-reactivity of individual T cells. Although virtual memory T cells descend from the highly self-reactive clones and acquire a partial memory program, they are not more potent in inducing experimental autoimmune diabetes than na{\"i}ve T cells. These data underline the importance of the variable level of self-reactivity in polyclonal T cells for the generation of functional T-cell diversity.",
keywords = "gene expression profiling of T-cell subsets, retrogenic T cell, self-reactivity, T-cell receptor repertoire, virtual memory T cells",
author = "Ales Drobek and Alena Moudra and Daniel Mueller and Martina Huranova and Veronika Horkova and Michaela Pribikova and Robert Ivanek and Susanne Oberle and Dietmar Zehn and McCoy, {Kathy D.} and Peter Draber and Ondrej Stepanek",
note = "Funding Information: We thank Prof. Alfred Signer for providing us with CD8.4 mice. We thank Ladi-slav Cupak, Barbara Hausmann, and Rosmarie Lang for their technical assistance and genotyping of mice. We thank Zdenek Cimburek and Matyas Sima for cell sorting. We thank Prof. Ed Palmer for his multisided support to the project. This project was supported by the Swiss National Science Foundation (Promys, IZ11Z0_166538), the Czech Science Foundation (GJ16-09208Y) to OS, ERC Starting Grant (ProtecTC) to DZ, and the Institute of Molecular Genetics (RVO 68378050). The animal facility of the IMG is a part of the Czech Centre for Phenogenomics and the work there was supported in part by following grants: LM2015040, OP RDI CZ.1.05/2.1.00/19.0395, OP RDI BIOCEV CZ.1.05/ 1.1.00/02.0109 provided by the Czech Ministry of Education, Youth, and Sports and the European Regional Development Fund. The Group of Adaptive Immunity at the Institute of Molecular Genetics in Prague is supported by an EMBO Installation grant. AM, VH, and MP are students of the Faculty of Science, Charles University, Prague. Funding Information: We thank Prof. Alfred Signer for providing us with CD8.4 mice. We thank Ladislav Cupak, Barbara Hausmann, and Rosmarie Lang for their technical assistance and genotyping of mice. We thank Zdenek Cimburek and Matyas Sima for cell sorting. We thank Prof. Ed Palmer for his multisided support to the project. This project was supported by the Swiss National Science Foundation (Promys, IZ11Z0_166538), the Czech Science Foundation (GJ16-09208Y) to OS, ERC Starting Grant (ProtecTC) to DZ, and the Institute of Molecular Genetics (RVO 68378050). The animal facility of the IMG is a part of the Czech Centre for Phenogenomics and the work there was supported in part by following grants: LM2015040, OP RDI CZ.1.05/2.1.00/19.0395, OP RDI BIOCEV CZ.1.05/1.1.00/02.0109 provided by the Czech Ministry of Education, Youth, and Sports and the European Regional Development Fund. The Group of Adaptive Immunity at the Institute of Molecular Genetics in Prague is supported by an EMBO Installation grant. AM, VH, and MP are students of the Faculty of Science, Charles University, Prague. Publisher Copyright: {\textcopyright} 2018 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2018",
month = jul,
day = "13",
doi = "10.15252/embj.201798518",
language = "English",
volume = "37",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "14",
}