High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival.

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Version: Final published version
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Serval ID
serval:BIB_B2EBEA9B2D32
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival.
Journal
The Journal of experimental medicine
Author(s)
Utzschneider D.T., Alfei F., Roelli P., Barras D., Chennupati V., Darbre S., Delorenzi M., Pinschewer D.D., Zehn D.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
22/08/2016
Peer-reviewed
Oui
Volume
213
Number
9
Pages
1819-1834
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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
Yes
Create date
28/07/2016 15:44
Last modification date
07/04/2021 5:34
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