Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells.
EMBO J
; 37(14)2018 07 13.
Article
in En
| MEDLINE
| ID: mdl-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Antigen, T-Cell
/
Cell Differentiation
/
CD8-Positive T-Lymphocytes
/
Immunologic Memory
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
EMBO J
Year:
2018
Type:
Article
Affiliation country:
Czech Republic