Alterations in CD39/CD73 axis of T cells associated with COVID‐19 severity

  1. Gilson P. Dorneles
  2. Paula C. Teixeira
  3. Igor M. da Silva
  4. Lucas L. Schipper
  5. Paulo C. Santana Filho
  6. Luiz C. Rodrigues Junior
  7. Cristina Bonorino
  8. Alessandra Peres
  9. Simone G. Fonseca
  10. Marta C. Monteiro
  11. Carina R. Boeck
  12. Sarah Eller
  13. Tiago F. Oliveira
  14. Eliana M. Wendland
  15. Pedro R. T. Romão

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in coronavirus disease 2019 (COVID‐19) patients. Mild and severe COVID‐19 patients had lower extracellular adenosine triphosphate and adenosine levels, and higher cytokines than healthy controls. Mild COVID‐19 patients presented lower frequencies of CD4 + CD25 + CD39 + (activated/memory regulatory T cell [mTreg]) and increased frequencies of high‐differentiated (CD27 − CD28 − ) CD8 + T cells compared with healthy controls. Severe COVID‐19 patients also showed higher frequencies of CD4 + CD39 + , CD4 + CD25 − CD39 + (memory T effector cell), and high‐differentiated CD8 + T cells (CD27 − CD28 − ), and diminished frequencies of CD4 + CD73 + , CD4 + CD25 + CD39 + mTreg cell, CD8 + CD73 + , and low‐differentiated CD8 + T cells (CD27 + CD28 + ) in the blood in relation to mild COVID‐19 patients and controls. Moreover, severe COVID‐19 patients presented higher expression of PD‐1 on low‐differentiated CD8 + T cells. Both severe and mild COVID‐19 patients presented higher frequencies of CD4 + Annexin‐V + and CD8 + Annexin‐V + T cells, indicating increased T‐cell apoptosis. Plasma samples collected from severe COVID‐19 patients were able to decrease the expression of CD73 on CD4 + and CD8 + T cells of a healthy donor. Interestingly, the in vitro incubation of peripheral blood mononuclear cell from severe COVID‐19 patients with adenosine reduced the nuclear factor‐κB activation in T cells and monocytes. Together, these data add new knowledge to the COVID‐19 immunopathology through purinergic regulation.

Article activity feed

  1. Version published to 10.1002/jcp.30805
  2. ScreenIT

    SciScore for 10.1101/2021.09.18.21263782: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: This study was approved by the Moinhos de Vento Ethics Committee N 3977144 (Porto Alegre/Brazil) and informed consent was obtained from all participants.
    Consent: This study was approved by the Moinhos de Vento Ethics Committee N 3977144 (Porto Alegre/Brazil) and informed consent was obtained from all participants.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The detection limits of each cytokine were IL□6, 2□200 pg/mL; IL□10, 2□300 pg/mL; IL□17A, 2□1000 pg/ mL; TGF-β, 20 – 500 pg/mL. 2.4 Immunophenotyping: Whole blood samples (100 µL) were incubated with monoclonal surface antibodies (all anti-human) at 4 °C for 20 min in accordance with the following combination: a) FITC-conjugated anti-CD4, Pe-conjugated anti-CD25, PerCP-Cy5.5-conjugated anti-CD39, APC-conjugated anti-CD73; b) FITC-conjugated anti-CD8, Pe-conjugated anti-CD39, APC-conjugated anti-CD73; c) PerCP-Cy5.5-conjugated anti-CD19, Pe-conjugated anti-CD39, APC-conjugated anti-CD73; d) FITC-conjugated anti-CD8, Pe-conjugated anti-CD28, PerCP-Cy5.5-conjugated anti-CD27, APC-conjugated anti-PD-1.
    anti-human) at 4
    suggested: None
    anti-CD4
    suggested: None
    anti-CD25
    suggested: None
    anti-CD73
    suggested: None
    anti-CD8
    suggested: (BD Biosciences Cat# 340031, RRID:AB_399998)
    anti-CD19
    suggested: None
    anti-CD39
    suggested: None
    anti-CD28
    suggested: None
    anti-CD27
    suggested: None
    anti-PD-1
    suggested: None
    Software and Algorithms
    SentencesResources
    The SPSS 20.0 (IBM Inc, EUA) software was used in all analysis.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.09.18.21263782 on medRxiv