CD39 expression identifies terminally exhausted [CD8.sup.+] T cells

• Published in: PLoS pathogens 2015-10
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Care and treatment; Development and progression; Gene expression; Hepatitis C; Prevention; Risk factors
• ISSN: 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1005177

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.sup.+] T cells. [CD8.sup.+] 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.sup.+] 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.sup.+] T cells contain a population of [CD39.sup.high] [CD8.sup.+] T cells that is absent in functional memory cells elicited by acute infection. This [CD39.sup.high] [CD8.sup.+] 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.