%0 Journal Article %J PLoS Pathog %D 2015 %T CD39 Expression Identifies Terminally Exhausted CD8+ T Cells. %A Gupta, Prakash K %A Godec, Jernej %A Wolski, David %A Adland, Emily %A Yates, Kathleen %A Pauken, Kristen E %A Cosgrove, Cormac %A Ledderose, Carola %A Junger, Wolfgang G %A Robson, Simon C %A Wherry, E John %A Alter, Galit %A Goulder, Philip J R %A Klenerman, Paul %A Sharpe, Arlene H %A Lauer, Georg M %A Haining, W Nicholas %K Animals %K Antigens, CD %K Apyrase %K Arenaviridae Infections %K Biomarkers %K CD8-Positive T-Lymphocytes %K Chromatography, High Pressure Liquid %K Chronic Disease %K Disease Models, Animal %K Flow Cytometry %K Hepatitis C, Chronic %K HIV Infections %K Humans %K Lymphocytic Choriomeningitis %K Lymphocytic choriomeningitis virus %K Mice %K Mice, Inbred C57BL %K Oligonucleotide Array Sequence Analysis %K RNA Virus Infections %K T-Lymphocyte Subsets %X 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. %B PLoS Pathog %V 11 %P e1005177 %8 2015 Oct %G eng %N 10 %1 http://www.ncbi.nlm.nih.gov/pubmed/26485519?dopt=Abstract %R 10.1371/journal.ppat.1005177