Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion.
CD39 Expression Identifies Terminally Exhausted CD8+ T Cells
P. Gupta,Jernej Godec,David Wolski,E. Adland,Kathleen B. Yates,Kristen E. Pauken,C. Cosgrove,Carola Ledderose,W. Junger,S. Robson,E. Wherry,G. Alter,P. Goulder,P. Klenerman,A. Sharpe,G. Lauer,W. Haining
Published 2015 in PLoS Pathogens
ABSTRACT
PUBLICATION RECORD
- Publication year
2015
- Venue
PLoS Pathogens
- Publication date
2015-10-01
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
- No claims are published for this paper.
CONCEPTS
- No concepts are published for this paper.
REFERENCES
Showing 1-58 of 58 references · Page 1 of 1