CD39 Expression Identifies Terminally Exhausted CD8+ T Cells.

PLoS Pathog
Authors
Keywords
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.

Year of Publication
2015
Journal
PLoS Pathog
Volume
11
Issue
10
Pages
e1005177
Date Published
2015 Oct
ISSN
1553-7374
DOI
10.1371/journal.ppat.1005177
PubMed ID
26485519
PubMed Central ID
PMC4618999
Links
Grant list
091663 / Wellcome Trust / United Kingdom
104748 / Wellcome Trust / United Kingdom
U19 AI082630 / AI / NIAID NIH HHS / United States