Cell-density independent increased lymphocyte production and loss rates post-autologous HSCT
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
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.
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
Reviewing Editor
- Frederik Graw, Heidelberg University, Germany
Publication history
- Received: June 8, 2020
- Accepted: February 3, 2021
- Accepted Manuscript published: February 4, 2021 (version 1)
- 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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