Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73- Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes

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@article{722857b6195a42cd96ec1a83a045fe91,
title = "Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73- Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes",
abstract = "The ectonucleotidases CD39 and CD73 regulate immune responses by balancing extracellular ATP and adenosine in inflammation and are likely to be involved in the pathophysiology of COVID-19. Here, we analyzed CD39 and CD73 on different lymphocyte populations in a small cohort of COVID-19 patients and in healthy individuals. We describe a significantly lower level of expression of CD73 on cytotoxic lymphocyte populations, including CD8+ T, natural killer T (NKT), and natural killer (NK) cells, during COVID-19. Interestingly, the decrease of CD73 on CD8+ T cells and NKT cells correlated with serum ferritin levels. Furthermore, we observed distinct functional differences between the CD73+ and CD73- subsets of CD8+ T cells and NKT cells with regard to cytokine/toxin secretion. In COVID-19 patients, the majority of the CD73-CD8+ T cells were capable of secreting granzyme B, perforin, tumor necrosis factor (TNF-α) or interferon-gamma (IFN-γ). To conclude, in this first study of CD39 and CD73 expression of lymphocytes in COVID-19, we show that CD8+ T cells and NKT cells lacking CD73 possess a significantly higher cytotoxic effector functionality compared to their CD73+ counterparts. Future studies should investigate differences of cellular CD39 and CD73 expression in patients at different disease stages and their potential as prognostic markers or targets for immunomodulatory therapies.",
keywords = "5'-Nucleotidase/metabolism, Adenosine/metabolism, Adult, Aged, Apyrase/metabolism, Betacoronavirus, Coronavirus Infections/enzymology, Female, GPI-Linked Proteins/metabolism, Granzymes/metabolism, Humans, Inflammation/enzymology, Interferon-gamma/metabolism, Killer Cells, Natural/immunology, Male, Middle Aged, Natural Killer T-Cells/immunology, Pandemics, Perforin/metabolism, Pneumonia, Viral/enzymology, Signal Transduction/immunology, T-Lymphocytes, Cytotoxic/immunology, Tumor Necrosis Factor-alpha/metabolism",
author = "Parimah Ahmadi and Philip Hartjen and Matin Kohsar and Silke Kummer and Stefan Schmiedel and Jan-Hendrik Bockmann and Anahita Fathi and Samuel Huber and Friedrich Haag and {Schulze Zur Wiesch}, Julian",
year = "2020",
month = jul,
day = "22",
doi = "10.3390/cells9081750",
language = "English",
volume = "9",
journal = "CELLS-BASEL",
issn = "2073-4409",
publisher = "MDPI Multidisciplinary Digital Publishing Institute",
number = "8",

}

RIS

TY - JOUR

T1 - Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73- Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes

AU - Ahmadi, Parimah

AU - Hartjen, Philip

AU - Kohsar, Matin

AU - Kummer, Silke

AU - Schmiedel, Stefan

AU - Bockmann, Jan-Hendrik

AU - Fathi, Anahita

AU - Huber, Samuel

AU - Haag, Friedrich

AU - Schulze Zur Wiesch, Julian

PY - 2020/7/22

Y1 - 2020/7/22

N2 - The ectonucleotidases CD39 and CD73 regulate immune responses by balancing extracellular ATP and adenosine in inflammation and are likely to be involved in the pathophysiology of COVID-19. Here, we analyzed CD39 and CD73 on different lymphocyte populations in a small cohort of COVID-19 patients and in healthy individuals. We describe a significantly lower level of expression of CD73 on cytotoxic lymphocyte populations, including CD8+ T, natural killer T (NKT), and natural killer (NK) cells, during COVID-19. Interestingly, the decrease of CD73 on CD8+ T cells and NKT cells correlated with serum ferritin levels. Furthermore, we observed distinct functional differences between the CD73+ and CD73- subsets of CD8+ T cells and NKT cells with regard to cytokine/toxin secretion. In COVID-19 patients, the majority of the CD73-CD8+ T cells were capable of secreting granzyme B, perforin, tumor necrosis factor (TNF-α) or interferon-gamma (IFN-γ). To conclude, in this first study of CD39 and CD73 expression of lymphocytes in COVID-19, we show that CD8+ T cells and NKT cells lacking CD73 possess a significantly higher cytotoxic effector functionality compared to their CD73+ counterparts. Future studies should investigate differences of cellular CD39 and CD73 expression in patients at different disease stages and their potential as prognostic markers or targets for immunomodulatory therapies.

AB - The ectonucleotidases CD39 and CD73 regulate immune responses by balancing extracellular ATP and adenosine in inflammation and are likely to be involved in the pathophysiology of COVID-19. Here, we analyzed CD39 and CD73 on different lymphocyte populations in a small cohort of COVID-19 patients and in healthy individuals. We describe a significantly lower level of expression of CD73 on cytotoxic lymphocyte populations, including CD8+ T, natural killer T (NKT), and natural killer (NK) cells, during COVID-19. Interestingly, the decrease of CD73 on CD8+ T cells and NKT cells correlated with serum ferritin levels. Furthermore, we observed distinct functional differences between the CD73+ and CD73- subsets of CD8+ T cells and NKT cells with regard to cytokine/toxin secretion. In COVID-19 patients, the majority of the CD73-CD8+ T cells were capable of secreting granzyme B, perforin, tumor necrosis factor (TNF-α) or interferon-gamma (IFN-γ). To conclude, in this first study of CD39 and CD73 expression of lymphocytes in COVID-19, we show that CD8+ T cells and NKT cells lacking CD73 possess a significantly higher cytotoxic effector functionality compared to their CD73+ counterparts. Future studies should investigate differences of cellular CD39 and CD73 expression in patients at different disease stages and their potential as prognostic markers or targets for immunomodulatory therapies.

KW - 5'-Nucleotidase/metabolism

KW - Adenosine/metabolism

KW - Adult

KW - Aged

KW - Apyrase/metabolism

KW - Betacoronavirus

KW - Coronavirus Infections/enzymology

KW - Female

KW - GPI-Linked Proteins/metabolism

KW - Granzymes/metabolism

KW - Humans

KW - Inflammation/enzymology

KW - Interferon-gamma/metabolism

KW - Killer Cells, Natural/immunology

KW - Male

KW - Middle Aged

KW - Natural Killer T-Cells/immunology

KW - Pandemics

KW - Perforin/metabolism

KW - Pneumonia, Viral/enzymology

KW - Signal Transduction/immunology

KW - T-Lymphocytes, Cytotoxic/immunology

KW - Tumor Necrosis Factor-alpha/metabolism

U2 - 10.3390/cells9081750

DO - 10.3390/cells9081750

M3 - SCORING: Journal article

C2 - 32707842

VL - 9

JO - CELLS-BASEL

JF - CELLS-BASEL

SN - 2073-4409

IS - 8

ER -