CD39 Expression Identifies Terminally Exhausted CD8+ T Cells
Gupta, Prakash K.
Pauken, Kristen E.
Wherry, E. John
Goulder, Philip J. R.
Haining, W. NicholasNote: Order does not necessarily reflect citation order of authors.
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CitationGupta, P. K., J. Godec, D. Wolski, E. Adland, K. Yates, K. E. Pauken, C. Cosgrove, et al. 2015. “CD39 Expression Identifies Terminally Exhausted CD8+ T Cells.” PLoS Pathogens 11 (10): e1005177. doi:10.1371/journal.ppat.1005177. http://dx.doi.org/10.1371/journal.ppat.1005177.
AbstractExhausted 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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