Temporal changes in T cell subsets and expansion of cytotoxic CD4+ T cells in the lungs in severe COVID-19

  1. Naoki Kaneko
  2. Julie Boucau
  3. Hsiao-Hsuan Kuo
  4. Cory Perugino
  5. Vinay S. Mahajan
  6. Jocelyn R. Farmer
  7. Hang Liu
  8. Thomas J. Diefenbach
  9. Alicja Piechocka-Trocha
  10. Kristina Lefteri
  11. Michael T. Waring
  12. Katherine R. Premo
  13. Bruce D. Walker
  14. Jonathan Z. Li
  15. Gaurav Gaiha
  16. Xu G. Yu
  17. Mathias Lichterfeld
  18. Robert F. Padera
  19. Shiv Pillai

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Abstract

No abstract available

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  1. Version published to 10.1016/j.clim.2022.108991
  2. ScreenIT

    SciScore for 10.1101/2021.03.23.21253885: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    These specimens were incubated with the following antibodies: anti-CD3 (A045229-2;
    anti-CD3
    suggested: (Agilent Cat# A0452, RRID:AB_2335677)
    Lifespan Bioscience) and anti-cleaved caspase-3 (9664; Cell Signaling Technology) followed by incubation with a secondary antibody using an Opal™ Multiplex Kit (Perkin Elmer).
    anti-cleaved caspase-3
    suggested: None
    Cells were surface stained at 4, protected from light, using optimized concentrations of fluorochrome-conjugated primary antibodies for 30 minutes as well as live/dead fixable blue stain (Thermo Fisher) at a concentration of 1:20 using the following antibody panels (clone, manufacturer): CD14 (HCD14, Biolegend), CD19 (HIB19, Biolegend), CD34 (581, Biolegend)
    CD14
    suggested: (BioLegend Cat# 348805, RRID:AB_2889063)
    CD19
    suggested: None
    HIB19
    suggested: None
    CD34
    suggested: None
    Additional antibodies used in this assay not included in the other blood studies included mouse anti-human CD69-BB700 (BD Bioscience, clone FN50, stained at 1:50 at 4C), mouse anti-human CD38-BUV661 (BD Bioscience, clone HIT2, stained at 1:400 at 37C), mouse anti-human CX3CR1-APC (BioLegend, clone 2A9-1, stained at 1:50 at 4C), and mouse anti-human CD28-BV480 (BD Bioscience, clone CD28.2, stained at 1:100 at 37C) Study Approval: This study was conducted with the approval of the Institutional Review Boards at the Massachusetts General Hospital and the Brigham and Women’s Hospital.
    anti-human CD69-BB700
    suggested: None
    anti-human CD38-BUV661
    suggested: None
    anti-human CX3CR1-APC
    suggested: None
    anti-human CD28-BV480
    suggested: None
    Software and Algorithms
    SentencesResources
    GraphPad Prism version 8 was used for statistical analysis, curve fitting and linear regression.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    FCS files were analyzed, and B cell subsets were quantified using FlowJo software (version 10)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    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: We detected the following sentences addressing limitations in the study:
    Limitations of the Study: Of necessity, the numbers for the autopsies of non-immunosuppressed patients from whom matched lungs and thoracic lymph nodes were studied were relatively small. While we studied rapidly conducted autopsies with preservation of tissue morphology, autopsy studies are by nature descriptive. Although numerous previous studies have shown the functional ability of CD4+CTLs to kill infected targets, these have all been on the blood, and we could not conduct cytotoxicity studies in the course of this project. We used a single approach to study lymphocyte populations in the lymph nodes and the spleen, and while the complementary use of an orthogonal approach would have been ideal, our data were broadly validated by an analysis of blood lymphocytes by us and by others who have analyzed antigen-specific CD4+ T cells in the blood in severe COVID-19

    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.

    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 10.1101/2021.03.23.21253885 on medRxiv