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

0495610 - ÚMG 2019 RIV GB eng J - Článek v odborném periodiku
Drobek, Aleš - Moudrá, Alena - Mueller, D. - Huranová, Martina - Horková, Veronika - Přibíková, Michaela - Ivánek, R. - Zehn, D. - Oberle, S. - McCoy, K.D. - Dráber, Peter - Štěpánek, Ondřej
Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells.
EMBO Journal. Roč. 37, č. 14 (2018), č. článku e98518. ISSN 0261-4189. E-ISSN 1460-2075
Grant CEP: GA ČR GJ16-09208Y; GA MŠMT(CZ) LM2015040; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) ED1.1.00/02.0109
Institucionální podpora: RVO:68378050
Klíčová slova: gene expression profiling of T-cell subsets * retrogenic T cell * self-reactivity * T-cell receptor repertoire * virtual memory T cells
Obor OECD: Immunology
Impakt faktor: 11.227, rok: 2018

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 naive 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 naive 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.
Trvalý link: http://hdl.handle.net/11104/0288552