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PLoS Pathog. 2015 Oct 20;11(10):e1005177. doi: 10.1371/journal.ppat.1005177. eCollection 2015 Oct.

CD39 Expression Identifies Terminally Exhausted CD8+ T Cells.

Author information

1
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
2
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America; Department of Microbiology and Immunobiology and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
3
Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Massachusetts, United States of America.
4
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
5
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
6
Department of Microbiology and Institute for Immunology, University of Pennsylvania Perelman School Medicine, Philadelphia, Pennsylvania, United States of America.
7
Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
8
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
9
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, Massachusetts, United States of America.
10
Department of Microbiology and Immunobiology and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
11
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America; Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

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.

PMID:
26485519
PMCID:
PMC4618999
DOI:
10.1371/journal.ppat.1005177
[Indexed for MEDLINE]
Free PMC Article

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