Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73- Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes
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Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73- Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes. / Ahmadi, Parimah; Hartjen, Philip; Kohsar, Matin; Kummer, Silke; Schmiedel, Stefan; Bockmann, Jan-Hendrik; Fathi, Anahita; Huber, Samuel; Haag, Friedrich; Schulze Zur Wiesch, Julian.
In: CELLS-BASEL, Vol. 9, No. 8, 22.07.2020.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -