CD39 Expression Identifies Terminally Exhausted CD8+ T Cells

0301 basic medicine 570 QH301-705.5 610 HIV Infections CD8-Positive T-Lymphocytes Lymphocytic Choriomeningitis Mice 03 medical and health sciences RNA Virus Infections Antigens, CD T-Lymphocyte Subsets Animals Arenaviridae Infections Humans Lymphocytic choriomeningitis virus Biology (General) Chromatography, High Pressure Liquid Oligonucleotide Array Sequence Analysis Apyrase RC581-607 Hepatitis C, Chronic Flow Cytometry 3. Good health Mice, Inbred C57BL Disease Models, Animal Chronic Disease Immunologic diseases. Allergy Biomarkers Research Article
DOI: 10.1371/journal.ppat.1005177 Publication Date: 2015-10-20T18:28:18Z
ABSTRACT
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.
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