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

• Main Authors: Parimah Ahmadi, Philip Hartjen, Matin Kohsar, Silke Kummer, Stefan Schmiedel, Jan-Hendrik Bockmann, Anahita Fathi, Samuel Huber, Friedrich Haag, Julian Schulze zur Wiesch
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Cells
• Subjects: COVID-19; purinergic signaling; CD73; CD39; cytotoxic lymphocytes; granzyme B
• Online Access: https://www.mdpi.com/2073-4409/9/8/1750
• ISSN: 2073-4409

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.