Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells.

Drobek, Ales; Moudra, Alena; Mueller, Daniel; Huranova, Martina; Horkova, Veronika; Pribikova, Michaela; Ivanek, Robert; Oberle, Susanne; Zehn, Dietmar; McCoy, Kathleen; Draber, Peter; Stepanek, Ondrej (2018). Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells. The EMBO Journal, 37(14) EMBO Press 10.15252/embj.201798518

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

UniBE Contributor:

McCoy, Kathleen

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1460-2075

Publisher:

EMBO Press

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

04 Feb 2019 09:49

Last Modified:

26 Oct 2019 01:34

Publisher DOI:

10.15252/embj.201798518

PubMed ID:

29752423

Uncontrolled Keywords:

T‐cell receptor repertoire gene expression profiling of T‐cell subsets retrogenic T cell self‐reactivity virtual memory T cells

BORIS DOI:

10.7892/boris.122998

URI:

https://boris.unibe.ch/id/eprint/122998

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