CD39 Expression Identifies Terminally Exhausted CD8+ T Cells

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...

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Vydáno v:	PLoS pathogens Ročník 11; číslo 10; s. e1005177
Hlavní autoři:	Gupta, Prakash K., Godec, Jernej, Wolski, David, Adland, Emily, Yates, Kathleen, Pauken, Kristen E., Cosgrove, Cormac, Ledderose, Carola, Junger, Wolfgang G., Robson, Simon C., Wherry, E. John, Alter, Galit, Goulder, Philip J. R., Klenerman, Paul, Sharpe, Arlene H., Lauer, Georg M., Haining, W. Nicholas
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 01.10.2015 Public Library of Science (PLoS)
Témata:	Adenosine Animals Antigens Antigens, CD - immunology Apyrase - immunology Arenaviridae Infections - immunology Biomarkers CD8-Positive T-Lymphocytes - immunology Chromatography, High Pressure Liquid Chronic Disease Disease Models, Animal Flow Cytometry Funding Hepatitis C, Chronic - immunology HIV HIV Infections - immunology Human immunodeficiency virus Humans Infections Laboratory animals Lymphocytes Lymphocytic Choriomeningitis - immunology Lymphocytic choriomeningitis virus - immunology Mice Mice, Inbred C57BL Oligonucleotide Array Sequence Analysis Pathogens Population RNA Virus Infections - immunology T cell receptors T-Lymphocyte Subsets - immunology Transcription factors Viral infections
ISSN:	1553-7374, 1553-7366, 1553-7374
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: PKG JG DW EJW GML PK AHS WNH. Performed the experiments: PKG JG DW KY KEP CC EA CL. Analyzed the data: PKG JG DW KY KEP EA. Contributed reagents/materials/analysis tools: WGJ SCR GA PJRG. Wrote the paper: PKG JG DW PK AHS GML WNH. The authors have declared that no competing interests exist.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1005177