High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival.
Détails
Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_B2EBEA9B2D32
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival.
Périodique
The Journal of experimental medicine
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Statut éditorial
Publié
Date de publication
22/08/2016
Peer-reviewed
Oui
Volume
213
Numéro
9
Pages
1819-1834
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Chronic infections induce T cells showing impaired cytokine secretion and up-regulated expression of inhibitory receptors such as PD-1. What determines the acquisition of this chronic phenotype and how it impacts T cell function remain vaguely understood. Using newly generated recombinant antigen variant-expressing chronic lymphocytic choriomeningitis virus (LCMV) strains, we uncovered that T cell differentiation and acquisition of a chronic or exhausted phenotype depend critically on the frequency of T cell receptor (TCR) engagement and less significantly on the strength of TCR stimulation. In fact, we noted that low-level antigen exposure promotes the formation of T cells with an acute phenotype in chronic infections. Unexpectedly, we found that T cell populations with an acute or chronic phenotype are maintained equally well in chronic infections and undergo comparable primary and secondary expansion. Thus, our observations contrast with the view that T cells with a typical chronic infection phenotype are severely functionally impaired and rapidly transition into a terminal stage of differentiation. Instead, our data unravel that T cells primarily undergo a form of phenotypic and functional differentiation in the early phase of a chronic LCMV infection without inheriting a net survival or expansion deficit, and we demonstrate that the acquired chronic phenotype transitions into the memory T cell compartment.
Pubmed
Open Access
Oui
Création de la notice
28/07/2016 16:44
Dernière modification de la notice
21/11/2022 9:24