Cell-density independent increased lymphocyte production and loss rates post-autologous HSCT

  1. Mariona Baliu Piqué
  2. Vera van Hoeven
  3. Julia Drylewicz
  4. Lotte E van der Wagen
  5. Anke Janssen
  6. Sigrid A Otto
  7. Menno C van Zelm
  8. Rob J de Boer
  9. Jürgen JHE Kuball
  10. Jose AM Borghans  Is a corresponding author
  11. Kiki Tesselaar  Is a corresponding author
  1. University Medical Center Utrecht, Netherlands
  2. Amsterdam UMC, Netherlands
  3. Monash University and Alfred Hospital, Australia
  4. Utrecht University, Netherlands

Abstract

Lymphocyte numbers need to be quite tightly regulated. It is generally assumed that lymphocyte production and lifespan increase homeostatically when lymphocyte numbers are low, and vice versa return to normal once cell numbers have normalized. This widely-accepted concept is largely based on experiments in mice, but is hardly investigated in vivo in humans. Here we quantified lymphocyte production and loss rates in vivo in patients 0.5-1 year after their autologous hematopoietic stem cell transplantation (autoHSCT). We indeed found that the production rates of most T-cell and B-cell subsets in autoHSCT-patients were 2 to 8-times higher than in healthy controls, but went hand in hand with a 3 to 9-fold increase in cell loss rates. Both rates also did not normalize when cell numbers did. This shows that increased lymphocyte production and loss rates occur even long after autoHSCT and can persist in the face of apparently normal cell numbers.

Data availability

All data analysed during this study are included in the manuscript Source data is added as separate files for Figure 2, 3, 4, 6,7 and 8.

Article and author information

Author details

  1. Mariona Baliu Piqué

    Center for Translational Immunology, University Medical Center Utrecht, Urecht, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9276-8839
  2. Vera van Hoeven

    Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands
    Competing interests
    No competing interests declared.
  3. Julia Drylewicz

    Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9434-8459
  4. Lotte E van der Wagen

    Department of Hematology, University Medical Center Utrecht, Urecht, Netherlands
    Competing interests
    No competing interests declared.
  5. Anke Janssen

    Center for Translational Immunology, University Medical Center Utrecht, Urecht, Netherlands
    Competing interests
    No competing interests declared.
  6. Sigrid A Otto

    Center for Translational Immunology, University Medical Center Utrecht, Urecht, Netherlands
    Competing interests
    No competing interests declared.
  7. Menno C van Zelm

    Department of Immunology and Pathology, Monash University and Alfred Hospital, Melbourne, Australia
    Competing interests
    No competing interests declared.
  8. Rob J de Boer

    Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2130-691X
  9. Jürgen JHE Kuball

    Department of Hematology, University Medical Center Utrecht, Urecht, Netherlands
    Competing interests
    Jürgen JHE Kuball, reports grants from Novartis, Miltenyi Biotech, and Gadeta. Is inventor on multiple patents dealing with γδ T-cell research, ligands, and isolation techniques, and is scientific co-founder and shareholder of Gadeta. (Patent number: 9546998, 9891211, 10324083, 10578609. Publication number: 20200368278, 20200363397, 20190271688, 2019020961, 201901692603, 20180188234, 20170319674, 20170174741, 20150050670)..
  10. Jose AM Borghans

    Central Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
    For correspondence
    J.A.M.Borghans@umcutrecht.nl
    Competing interests
    No competing interests declared.
  11. Kiki Tesselaar

    Center for Translational Immunology, University Medical Center Utrecht, Urecht, Netherlands
    For correspondence
    K.Tesselaar@umcutrecht.nl
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9847-0814

Funding

European Union Seventh Framework Programme (FP7-PEOPLE-2012-ITN 317040-QuanTI)

  • Mariona Baliu Piqué

Landsteiner Foundation for Blood Transfusion Research (LSBR grant 0812)

  • Vera van Hoeven

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Frederik Graw, Heidelberg University, Germany

Ethics

Human subjects: This study was approved by the medical ethical committee of the University Medical CenterUtrecht and conducted in accordance with the Helsinki Declaration. Six patients who received an autoHSCT for the treatment of a hematologic malignancy were enrolled in the study after having provided written informed consent

Version history

  1. Received: June 8, 2020
  2. Accepted: February 3, 2021
  3. Accepted Manuscript published: February 4, 2021 (version 1)
  4. Version of Record published: February 16, 2021 (version 2)

Copyright

© 2021, Baliu Piqué et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Mariona Baliu Piqué
  2. Vera van Hoeven
  3. Julia Drylewicz
  4. Lotte E van der Wagen
  5. Anke Janssen
  6. Sigrid A Otto
  7. Menno C van Zelm
  8. Rob J de Boer
  9. Jürgen JHE Kuball
  10. Jose AM Borghans
  11. Kiki Tesselaar
(2021)
Cell-density independent increased lymphocyte production and loss rates post-autologous HSCT
eLife 10:e59775.
https://doi.org/10.7554/eLife.59775

Share this article

https://doi.org/10.7554/eLife.59775

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