Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells.
Publisher DOI
PubMed ID
29752423
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 naïve 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 naïve 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.
Date Issued
2018-07-13
Publication Type
Article
Subject(s)
Subjects
T‐cell receptor repertoire gene expression profiling of T‐cell subsets retrogenic T cell self‐reactivity virtual memory T cells
Language(s)
en
Author(s)
Drobek, Ales | |
Moudra, Alena | |
Mueller, Daniel | |
Huranova, Martina | |
Horkova, Veronika | |
Pribikova, Michaela | |
Ivanek, Robert | |
Oberle, Susanne | |
Zehn, Dietmar | |
Draber, Peter | |
Stepanek, Ondrej |
Journal
The EMBO Journal
Publisher
EMBO Press
ISSN
1460-2075
Access(Rights)
open.access