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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
CD39 Expression Identifies Terminally Exhausted CD8+ T Cells
PLoS Pathogens, Volume 11, No. 10, Article e1005177, Year 2015
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Description
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. © 2015 Gupta et al.
Authors & Co-Authors
Adland, Emily
United Kingdom, Oxford
University of Oxford
Cosgrove, Cormac P.
United States, Cambridge
Harvard University
Junger, Wolfgang Georg
United States, Boston
Beth Israel Deaconess Medical Center
Robson, Simon Christopher
United States, Boston
Beth Israel Deaconess Medical Center
Wherry, Edward John
United States, Philadelphia
University of Pennsylvania
Alter, Galit
United States, Cambridge
Harvard University
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
University of Oxford
Klenerman, Paul
United Kingdom, Oxford
University of Oxford
Lauer, Georg M.
United States, Boston
Harvard Medical School
Statistics
Citations: 245
Authors: 9
Affiliations: 7
Identifiers
Doi:
10.1371/journal.ppat.1005177
ISSN:
15537366
Research Areas
Infectious Diseases
Study Design
Cross Sectional Study