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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.

Original publication

DOI

10.1371/journal.ppat.1005177

Type

Journal article

Journal

PLoS Pathog

Publication Date

10/2015

Volume

11

Keywords

Animals, Antigens, CD, Apyrase, Arenaviridae Infections, Biomarkers, CD8-Positive T-Lymphocytes, Chromatography, High Pressure Liquid, Chronic Disease, Disease Models, Animal, Flow Cytometry, HIV Infections, Hepatitis C, Chronic, Humans, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Mice, Inbred C57BL, Oligonucleotide Array Sequence Analysis, RNA Virus Infections, T-Lymphocyte Subsets