Reduced mitochondrial respiration in peripheral T cells after paediatric heamatopoietic stem cell transplantation

Kasper Mølgaard*, Katrine Kielsen, Marianne Ifversen, Özcan Met, Inge Marie Svane, Klaus Müller

*Corresponding author for this work

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Abstract

Background: Recovery and functional differentiation of T-cell subsets are central for the development of immune function and complications after allogeneic hematopoietic stem cell transplantation (HSCT), but little is known about the cellular respiration and factors influencing T-cell metabolic fitness during immune maturation after HSCT. Method: We included 20 HSCT patients and analysed mitochondrial oxidative phosphorylation and mitochondrial fitness in peripheral blood mononuclear cell samples collected at days +90 and +180 after HSCT. Results: Phenotypic analysis revealed lower overall T-cell counts, lower CD4+/CD8+ ratio and a skewed distribution of early T-cell subsets at day +90, gradually recovering by day +180. Although ATP turnover in HSCT patients was similar to healthy controls, the spare respiratory capacity (SRC) of T cells, reflecting the available energy reserve, was significantly reduced at day +90 and +180 compared to healthy controls. This reduction in SRC was not correlated with the occurrence of acute graft-versus-host disease (aGVHD), the intensity of conditioning regimens and markers of T-cell exhaustion. Conclusion: We found significantly depressed SRC until six months post-HSCT, but we were not able to identify transplant-related risk factors or associations with the clinical outcome.

Original languageEnglish
Article number1327977
JournalFrontiers in Immunology
Volume14
ISSN1664-3224
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 Mølgaard, Kielsen, Ifversen, Met, Svane and Müller.

Keywords

  • acute graft-versus-host disease
  • hematopoietic stem cell transplantation
  • mitochondrial fitness
  • real-time metabolism
  • spare respiratory capacity
  • T cells

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