CD39 Expression Identifies Terminally Exhausted CD8+ T Cells.

• Main Authors: Prakash K Gupta, Jernej Godec, David Wolski, Emily Adland, Kathleen Yates, Kristen E Pauken, Cormac Cosgrove, Carola Ledderose, Wolfgang G Junger, Simon C Robson, E John Wherry, Galit Alter, Philip J R Goulder, Paul Klenerman, Arlene H Sharpe, Georg M Lauer, W Nicholas Haining
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2015-10-01
• Series: PLoS Pathogens
• Online Access: http://europepmc.org/articles/PMC4618999?pdf=render

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.