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Open AccessArticle

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

1
First Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
2
Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
3
German Center for Infection Research, Hamburg-Lübeck-Borstel-Riems, 23538 Lübeck, Germany
4
Department of Immunology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(8), 1750; https://doi.org/10.3390/cells9081750
Received: 7 June 2020 / Revised: 7 July 2020 / Accepted: 19 July 2020 / Published: 22 July 2020
(This article belongs to the Special Issue Regulation of Cytokine Signaling in Immunity)
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. View Full-Text
Keywords: COVID-19; purinergic signaling; CD73; CD39; cytotoxic lymphocytes; granzyme B; perforin; SARS-CoV-2; cytokines COVID-19; purinergic signaling; CD73; CD39; cytotoxic lymphocytes; granzyme B; perforin; SARS-CoV-2; cytokines
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MDPI and ACS Style

Ahmadi, P.; Hartjen, P.; Kohsar, M.; Kummer, S.; Schmiedel, S.; Bockmann, J.-H.; Fathi, A.; Huber, S.; Haag, F.; Schulze zur Wiesch, J. Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73- Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes. Cells 2020, 9, 1750.

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