T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

Details

Serval ID
serval:BIB_F1317F9BECF7
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?
Journal
Nature Reviews. Immunology
Author(s)
Speiser D.E., Utzschneider D.T., Oberle S.G., Münz C., Romero P., Zehn D.
ISSN
1474-1741 (Electronic)
ISSN-L
1474-1733
Publication state
Published
Issued date
2014
Volume
14
Number
11
Pages
768-774
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
Chronic viral infections and malignant tumours induce T cells that have a reduced ability to secrete effector cytokines and have upregulated expression of the inhibitory receptor PD1 (programmed cell death protein 1). These features have so far been considered to mark terminally differentiated 'exhausted' T cells. However, several recent clinical and experimental observations indicate that phenotypically exhausted T cells can still mediate a crucial level of pathogen or tumour control. In this Opinion article, we propose that the exhausted phenotype results from a differentiation process in which T cells stably adjust their effector capacity to the needs of chronic infection. We argue that this phenotype is optimized to cause minimal tissue damage while still mediating a critical level of pathogen control. In contrast to the presently held view of functional exhaustion, this new concept better reflects the pathophysiology and clinical manifestations of persisting infections, and it provides a rationale for emerging therapies that enhance T cell activity in chronic infection and cancer by blocking inhibitory receptors.
Pubmed
Web of science
Create date
27/10/2014 16:13
Last modification date
20/08/2019 17:18
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